Using C. Elegans to decipher the cellular and molecular mechanisms underlying neurodevelopmental disorders

Molecular Neurobiology

Volumn 48, Issue 3, 2013, Pages 465-489

  Bessa, Carlos ^a,b   Maciel, Patrícia ^a,b   Rodrigues, Ana João ^a,b  

^a UNIVERSITY OF MINHO   (Portugal)

^b UNIVERSITY OF MINHO   (Portugal)

Author keywords

Autism; C. Elegans; Epilepsy; Intellectual disability; Neurodevelopment

Indexed keywords

4 AMINOBUTYRIC ACID; ACETYLCHOLINE; COMPLEMENTARY RNA; NEUREXIN; NEUROLIGIN; PRESENILIN; SYNAPTOBREVIN;

AGYRIA; ALZHEIMER DISEASE; AUTISM; CAENORHABDITIS ELEGANS; CELLULAR PARAMETERS; DISEASE ASSOCIATION; DOWN SYNDROME; DROSOPHILA; FRONTAL LOBE EPILEPSY; GENE FUNCTION; GENE MUTATION; GENETIC ASSOCIATION; GENETIC MANIPULATION; HUMAN; INTELLECTUAL IMPAIRMENT; LEARNING; MEMORY; MOLECULAR MECHANICS; NERVE CELL NETWORK; NEUROLOGIC DISEASE; NONHUMAN; PARKINSON DISEASE; REVIEW;

ANIMALS; CAENORHABDITIS ELEGANS; DISEASE MODELS, ANIMAL; HUMANS; MEMORY; NERVOUS SYSTEM; NERVOUS SYSTEM DISEASES; SOCIAL BEHAVIOR;

EID: 84887996709     PISSN: 08937648     EISSN: 15591182     Source Type: Journal    
DOI: 10.1007/s12035-013-8434-6     Document Type: Review

References (298)

1. Bessa C, Lopes F, Maciel P, Molecular genetics of intellectual disability, InTech, Editor 2012
2. Abrams TW (2012) Studies on aplysia neurons suggest treatments for chronic human disorders. Curr Biol 22(17):R705-11
3. Gatto CL, Broadie K (2011) Drosophila modeling of heritable neurodevelopmental disorders. Curr Opin Neurobiol 21(6):834-41
4. Kabashi E et al (2010) In the swim of things: recent insights to neurogenetic disorders from zebrafish. Trends Genet 26(8):373-81
5. Wormbook. Available from: http://www.wormbook.org/
6. Wormatlas. Available from: http://www.wormatlas.org/
7. Bono MD, Villu Maricq A (2005) Neuronal substrates of complex behaviors in C. Elegans. Annu Rev Neurosci 28(1):451-501
8. Chalfie M et al (1994) Green fluorescent protein as a marker for gene expression. Science 263(5148):802-5
9. Hobert O, Loria P (2006) Uses of GFP in Caenorhabditis elegans. Methods Biochem Anal 47:203-26
10. White JG et al (1986) The structure of the nervous system of the nematode Caenorhabditis elegans. Philos Trans R Soc Lond B Biol Sci 314(1165):1-340
11. Jin, Y.; Synaptogenesis. WormBook, 2005: p. 1-11
12. Nonet ML (1999) Visualization of synaptic specializations in live C. Elegans with synaptic vesicle protein-GFP fusions. J Neurosci Methods 89(1):33-40
13. Dittman JS, Kaplan JM (2006) Factors regulating the abundance and localization of synaptobrevin in the plasma membrane. Proc Natl Acad Sci USA 103(30):11399-404
14. Jin Y et al (1999) The Caenorhabditis elegans gene unc-25 encodes glutamic acid decarboxylase and is required for synaptic transmission but not synaptic development. J Neurosci 19(2):539-48
15. Vashlishan AB et al (2008) An RNAi screen identifies genes that regulate GABA synapses. Neuron 58(3):346-361
16. Zhen M, Jin Y (1999) The liprin protein SYD-2 regulates the differentiation of presynaptic termini in C. Elegans. Nature 401(6751):371-5
17. Yeh E et al (2005) Identification of genes involved in synaptogenesis using a fluorescent active zone marker in Caenorhabditis elegans. J Neurosci 25(15):3833-41
18. Stigloher C et al (2011) The presynaptic dense projection of the Caenorhabditis elegans cholinergic neuromuscular junction localizes synaptic vesicles at the active zone through SYD-2/liprin and UNC-10/RIM-dependent interactions. J Neurosci 31(12):4388-96
19. Hall DH, Russell RL (1991) The posterior nervous system of the nematode Caenorhabditis elegans: serial reconstruction of identified neurons and complete pattern of synaptic interactions. J Neurosci 11(1):1-22
20. Zhao H, Nonet ML (2000) A retrograde signal is involved in activity-dependent remodeling at a C. Elegans neuromuscular junction. Development 127(6):1253-66
21. Rand, J.B.; Acetylcholine. WormBook, 2007: p. 1-21
22. Sieburth D et al (2005) Systematic analysis of genes required for synapse structure and function. Nature 436(7050):510-7
23. Brockie PJ et al (2001) Differential expression of glutamate receptor subunits in the nervous system of Caenorhabditis elegans and their regulation by the homeodomain protein UNC-42. J Neurosci 21(5):1510-22
24. Brockie, P.J. and A.V. Maricq, Ionotropic glutamate receptors: genetics, behavior and electrophysiology. WormBook, 2006: p. 1-16
25. Brockie PJ, Maricq AV (2003) Ionotropic glutamate receptors in Caenorhabditis elegans. Neurosignals 12(3):108-25
26. Cully DF et al (1994) Cloning of an avermectin-sensitive glutamate-gated chloride channel from Caenorhabditis elegans. Nature 371(6499):707-11
27. Avery L (1993) The genetics of feeding in Caenorhabditis elegans. Genetics 133(4):897-917
28. Lee RY et al (1999) EAT-4, a homolog of a mammalian sodium-dependent inorganic phosphate cotransporter, is necessary for glutamatergic neurotransmission in Caenorhabditis elegans. J Neurosci 19(1):159-67
29. Rankin CH, Wicks SR (2000) Mutations of the Caenorhabditis elegans brain-specific inorganic phosphate transporter eat-4 affect habituation of the tap-withdrawal response without affecting the response itself. J Neurosci 20(11):4337-44
30. Rose JK, Kaun KR, Rankin CH (2002) A new group-training procedure for habituation demonstrates that presynaptic glutamate release contributes to long-term memory in Caenorhabditis elegans. Learn Mem 9(3):130-7
31. Lee D et al (2008) Human vesicular glutamate transporters functionally complement EAT-4 in C. Elegans. Mol Cells 25(1):50-4
32. Morrison GE, van der Kooy D (2001) A mutation in the AMPA-type glutamate receptor, glr-1, blocks olfactory associative and nonassociative learning in Caenorhabditis elegans. Behav Neurosci 115(3):640-9
33. Chase, D.L. and M.R. Koelle, Biogenic amine neurotransmitters in C. Elegans. WormBook, 2007: p. 1-15
34. Chase DL, Pepper JS, Koelle MR (2004) Mechanism of extrasynaptic dopamine signaling in Caenorhabditis elegans. Nat Neurosci 7(10):1096-103
35. Cao S et al (2005) Torsin-mediated protection from cellular stress in the dopaminergic neurons of Caenorhabditis elegans. J Neurosci 25(15):3801-12
36. Marvanova M, Nichols CD (2007) Identification of neuroprotective compounds of Caenorhabditis elegans dopaminergic neurons against 6-OHDA. J Mol Neurosci 31(2):127-37
37. Nass R, Blakely RD (2003) The Caenorhabditis elegans dopaminergic system: opportunities for insights into dopamine transport and neurodegeneration. Annu Rev Pharmacol Toxicol 43:521-44
38. Jorgensen, E.M.; Gaba. WormBook, 2005: p. 1-13
39. Beg AA, Jorgensen EM (2003) EXP-1 is an excitatory GABA-gated cation channel. Nat Neurosci 6(11):1145-52
40. Bamber BA et al (2005) The composition of the GABA receptor at the Caenorhabditis elegans neuromuscular junction. Br J Pharmacol 144(4):502-9
41. Bamber BA, Twyman RE, Jorgensen EM (2003) Pharmacological characterization of the homomeric and heteromeric UNC-49 GABA receptors in C. Elegans. Br J Pharmacol 138(5):883-93
42. Schuske K, Beg AA, Jorgensen EM (2004) The GABA nervous system in C. Elegans. Trends Neurosci 27(7):407-14
43. Li, C. and K. Kim, Neuropeptides. WormBook, 2008: p. 1-36
44. Pierce SB et al (2001) Regulation of DAF-2 receptor signaling by human insulin and ins-1, a member of the unusually large and diverse C. Elegans insulin gene family. Genes Dev 15(6):672-86
45. Li W, Kennedy SG, Ruvkun G (2003) daf-28 encodes a C. Elegans insulin superfamily member that is regulated by environmental cues and acts in the DAF-2 signaling pathway. Genes Dev 17(7):844-58
46. Clancy DJ et al (2001) Extension of life-span by loss of CHICO, a Drosophila insulin receptor substrate protein. Science 292(5514):104-6
47. Tatar M et al (2001) A mutant Drosophila insulin receptor homolog that extends life-span and impairs neuroendocrine function. Science 292(5514):107-10
48. Holzenberger M et al (2003) IGF-1 receptor regulates lifespan and resistance to oxidative stress in mice. Nature 421(6919):182-7
49. Choy RK, Kemner JM, Thomas JH (2006) Fluoxetine-resistance genes in Caenorhabditis elegans function in the intestine and may act in drug transport. Genetics 172(2):885-92
50. Choy RK, Thomas JH (1999) Fluoxetine-resistant mutants in C. Elegans define a novel family of transmembrane proteins. Mol Cell 4(2):143-52
51. Weinshenker D, Garriga G, Thomas JH (1995) Genetic and pharmacological analysis of neurotransmitters controlling egg laying in C. Elegans. J Neurosci 15(10):6975-85
52. Ward A et al (2009) Cocaine modulates locomotion behavior in C. Elegans. PLoS One 4(6):e5946
53. Artal-Sanz M, de Jong L, Tavernarakis N (2006) Caenorhabditis elegans: a versatile platform for drug discovery. Biotechnol J 1(12):1405-18
54. Culotti JG, Russell RL (1978) Osmotic avoidance defective mutants of the nematode Caenorhabditis elegans. Genetics 90(2):243-56
55. Wheeler JM, Thomas JH (2006) Identification of a novel gene family involved in osmotic stress response in Caenorhabditis elegans. Genetics 174(3):1327-36
56. Hart AC et al (1999) Distinct signaling pathways mediate touch and osmosensory responses in a polymodal sensory neuron. J Neurosci 19(6):1952-8
57. Bargmann CI, Horvitz HR (1991) Chemosensory neurons with overlapping functions direct chemotaxis to multiple chemicals in C. Elegans. Neuron 7(5):729-42
58. Sambongi Y et al (2000) Caenorhabditis elegans senses protons through amphid chemosensory neurons: proton signals elicit avoidance behavior. NeuroReport 11(10):2229-32
59. Zhang Y, Lu H, Bargmann CI (2005) Pathogenic bacteria induce aversive olfactory learning in Caenorhabditis elegans. Nature 438(7065):179-84
60. Apfeld J, Kenyon C (1999) Regulation of lifespan by sensory perception in Caenorhabditis elegans. Nature 402(6763):804-9
61. Libert S et al (2007) Regulation of Drosophila life span by olfaction and food-derived odors. Science 315(5815):1133-7
62. Steidl S, Rose JK, Rankin CH (2003) Stages of memory in the nematode Caenorhabditis elegans. Behav Cogn Neurosci Rev 2(1):3-14
63. Lin, C.H. and C.H. Rankin, Nematode learning and memory: neuroethology, in Encyclopedia of animal behavior, D.B. Editors-in-Chief:Michael and M. Janice, Editors. 2010, Academic: Oxford. p. 520-526
64. Mohri A et al (2005) Genetic control of temperature preference in the nematode Caenorhabditis elegans. Genetics 169(3):1437-50
65. Wen JY et al (1997) Mutations that prevent associative learning in C. Elegans. Behav Neurosci 111(2):354-68
66. Hukema RK et al (2006) Antagonistic sensory cues generate gustatory plasticity in Caenorhabditis elegans. EMBO J 25(2):312-22
67. Jansen G, Weinkove D, Plasterk RH (2002) The G-protein gamma subunit gpc-1 of the nematode C. Elegans is involved in taste adaptation. EMBO J 21(5):986-94
68. Mori I, Ohshima Y (1995) Neural regulation of thermotaxis in Caenorhabditis elegans. Nature 376(6538):344-8
69. Saeki S, Yamamoto M, Iino Y (2001) Plasticity of chemotaxis revealed by paired presentation of a chemoattractant and starvation in the nematode Caenorhabditis elegans. J Exp Biol 204(Pt 10):1757-64
70. Rose JK et al (2003) GLR-1, a non-NMDA glutamate receptor homolog, is critical for long-term memory in Caenorhabditis elegans. J Neurosci 23(29):9595-9
71. Beck CD, Rankin CH (1997) Long-term habituation is produced by distributed training at long ISIs and not by massed training or short ISIs in Caenorhabditis elegans. Anim Learn Behav 25(4):446-457
72. de Bono M, Bargmann CI (1998) Natural variation in a neuropeptide Y receptor homolog modifies social behavior and food response in C. Elegans. Cell 94(5):679-689
73. Lin S, Boey D, Herzog H (2004) NPY and Y receptors: lessons from transgenic and knockout models. Neuropeptides 38(4):189-200
74. Thorsell A et al (2006) The effects of social isolation on neuropeptide Y levels, exploratory and anxiety-related behaviors in rats. Pharmacol Biochem Behav 83(1):28-34
75. Aydin C, Oztan O, Isgor C (2011) Effects of a selective Y2R antagonist, JNJ-31020028, on nicotine abstinence-related social anxiety-like behavior, neuropeptide Y and corticotropin releasing factor mRNA levels in the novelty-seeking phenotype. Behav Brain Res 222(2):332-41
76. Timmons L, Court DL, Fire A (2001) Ingestion of bacterially expressed dsRNAs can produce specific and potent genetic interference in Caenorhabditis elegans. Gene 263(1-2):103-12
77. Simmer F et al (2002) Loss of the putative RNA-directed RNA polymerase RRF-3 makes C. Elegans hypersensitive to RNAi. Curr Biol 12(15):1317-9
78. Esposito G et al (2007) Efficient and cell specific knock-down of gene function in targeted C. Elegans neurons. Gene 395(1-2):170-6
79. Tavernarakis N et al (2000) Heritable and inducible genetic interference by double-stranded RNA encoded by transgenes. Nat Genet 24(2):180-3
80. Kerr R et al (2000) Optical imaging of calcium transients in neurons and pharyngeal muscle of C. Elegans. Neuron 26(3):583-94
81. Kuhara A et al (2008) Temperature sensing by an olfactory neuron in a circuit controlling behavior of C. Elegans. Science 320(5877):803-7
82. Nishida Y et al (2011) Identification of the AFD neuron as the site of action of the CREB protein in Caenorhabditis elegans thermotaxis. EMBO Rep 12(8):855-62
83. Schafer, W.R.; Neurophysiological methods in C. Elegans: an introduction. WormBook, 2006: p. 1-4
84. Francis MM, Mellem JE, Maricq AV (2003) Bridging the gap between genes and behavior: recent advances in the electrophysiological analysis of neural function in Caenorhabditis elegans. Trends Neurosci 26(2):90-9
85. Nonet ML et al (1998) Synaptic transmission deficits in Caenorhabditis elegans synaptobrevin mutants. J Neurosci 18(1):70-80
86. Dent JA, Davis MW, Avery L (1997) avr-15 encodes a chloride channel subunit that mediates inhibitory glutamatergic neurotransmission and ivermectin sensitivity in Caenorhabditis elegans. EMBO J 16(19):5867-79
87. Nickell WT et al (2002) Single ionic channels of two Caenorhabditis elegans chemosensory neurons in native membrane. J Membr Biol 189(1):55-66
88. O'Hagan R, Chalfie M, Goodman MB (2005) The MEC-4 DEG/ENaC channel of Caenorhabditis elegans touch receptor neurons transduces mechanical signals. Nat Neurosci 8(1):43-50
89. Richmond JE, Jorgensen EM (1999) One GABA and two acetylcholine receptors function at the C. Elegans neuromuscular junction. Nat Neurosci 2(9):791-7
90. Mellem JE et al (2002) Decoding of polymodal sensory stimuli by postsynaptic glutamate receptors in C. Elegans. Neuron 36(5):933-44
91. Goodman MB et al (1998) Active currents regulate sensitivity and dynamic range in C. Elegans neurons. Neuron 20(4):763-72
92. Lockery SR, Goodman MB (1998) Tight-seal whole-cell patch clamping of Caenorhabditis elegans neurons. Methods Enzymol 293:201-17
93. Wicks SR, Rankin CH (1995) Integration of mechanosensory stimuli in Caenorhabditis elegans. J Neurosci 15(3 Pt 2):2434-44
94. Wicks SR, Rankin CH (1996) The integration of antagonistic reflexes revealed by laser ablation of identified neurons determines habituation kinetics of the Caenorhabditis elegans tap withdrawal response. J Comp Physiol A 179(5):675-85
95. Chung SH et al (2006) The role of the AFD neuron in C. Elegans thermotaxis analyzed using femtosecond laser ablation. BMC Neurosci 7:30
96. Kimura KD et al (2004) The C. Elegans thermosensory neuron AFD responds to warming. Curr Biol 14(14):1291-5
97. Chalfie M et al (1985) The neural circuit for touch sensitivity in Caenorhabditis elegans. J Neurosci 5(4):956-64
98. Harbinder S et al (1997) Genetically targeted cell disruption in Caenorhabditis elegans. Proc Natl Acad Sci USA 94(24):13128-33
99. Qi YB et al (2012) Photo-inducible cell ablation in Caenorhabditis elegans using the genetically encoded singlet oxygen generating protein miniSOG. Proc Natl Acad Sci USA 109(19):7499-504
100. Byrne, A.B.; T.J. Edwards, and M. Hammarlund, In vivo laser axotomy in C. Elegans. J Vis Exp, 2011(51)
101. Hammarlund M et al (2009) Axon regeneration requires a conserved MAP kinase pathway. Science 323(5915):802-6
102. Zhang F et al (2007) Multimodal fast optical interrogation of neural circuitry. Nature 446(7136):633-9
103. Li W et al (2011) The neural circuits and sensory channels mediating harsh touch sensation in Caenorhabditis elegans. Nat Commun 2:315
104. Lindsay TH, Thiele TR, Lockery SR (2011) Optogenetic analysis of synaptic transmission in the central nervous system of the nematode Caenorhabditis elegans. Nat Commun 2:306
105. Liewald JF et al (2008) Optogenetic analysis of synaptic function. Nat Methods 5(10):895-902
106. Stirman JN et al (2010) High-throughput study of synaptic transmission at the neuromuscular junction enabled by optogenetics and microfluidics. J Neurosci Methods 191(1):90-3
107. Leifer AM et al (2011) Optogenetic manipulation of neural activity in freely moving Caenorhabditis elegans. Nat Methods 8(2):147-52
108. Okazaki A, Sudo Y, Takagi S (2012) Optical silencing of C. Elegans cells with arch proton pump. PLoS One 7(5):e35370
109. Caceres Ide C et al (2012) Laterally orienting C. Elegans using geometry at microscale for high-throughput visual screens in neurodegeneration and neuronal development studies. PLoS One 7(4):e35037
110. Shaye DD, Greenwald I (2011) OrthoList: a compendium of C. Elegans genes with human orthologs. PLoS One 6(5):e20085
111. Kraemer BC et al (2006) Molecular pathways that influence human tau-induced pathology in Caenorhabditis elegans. Hum Mol Genet 15(9):1483-96
112. Kraemer BC et al (2003) Neurodegeneration and defective neurotransmission in a Caenorhabditis elegans model of tauopathy. Proc Natl Acad Sci USA 100(17):9980-5
113. Levitan D et al (1996) Assessment of normal and mutant human presenilin function in Caenorhabditis elegans. Proc Natl Acad Sci USA 93(25):14940-4
114. Link CD et al (2003) Gene expression analysis in a transgenic Caenorhabditis elegans Alzheimer's disease model. Neurobiol Aging 24(3):397-413
115. Wittenburg N et al (2000) Presenilin is required for proper morphology and function of neurons in C. Elegans. Nature 406(6793):306-9
116. Hamamichi S et al (2008) Hypothesis-based RNAi screening identifies neuroprotective genes in a Parkinson's disease model. Proc Natl Acad Sci USA 105(2):728-33
117. Vartiainen S et al (2006) Identification of gene expression changes in transgenic C. Elegans overexpressing human alpha-synuclein. Neurobiol Dis 22(3):477-86
118. Teixeira-Castro A et al (2011) Neuron-specific proteotoxicity of mutant ataxin-3 in C. Elegans: rescue by the DAF-16 and HSF-1 pathways. Hum Mol Genet 20(15):2996-3009
119. Faber PW et al (1999) Polyglutamine-mediated dysfunction and apoptotic death of a Caenorhabditis elegans sensory neuron. Proc Natl Acad Sci USA 96(1):179-84
120. Satyal SH et al (2000) Polyglutamine aggregates alter protein folding homeostasis in Caenorhabditis elegans. Proc Natl Acad Sci USA 97(11):5750-5
121. Rodrigues AJ et al (2007) Functional genomics and biochemical characterization of the C. Elegans orthologue of the Machado-Joseph disease protein ataxin-3. FASEB J 21(4):1126-36
122. Rodrigues AJ et al (2009) ATX-3, CDC-48 and UBXN-5: a new trimolecular complex in Caenorhabditis elegans. Biochem Biophys Res Commun 386(4):575-81
123. de Voer G et al (2005) Deletion of the Caenorhabditis elegans homologues of the CLN3 gene, involved in human juvenile neuronal ceroid lipofuscinosis, causes a mild progeric phenotype. J Inherit Metab Dis 28(6):1065-80
124. Oeda T et al (2001) Oxidative stress causes abnormal accumulation of familial amyotrophic lateral sclerosis-related mutant SOD1 in transgenic Caenorhabditis elegans. Hum Mol Genet 10(19):2013-23
125. Baumeister R, Ge L (2002) The worm in us - Caenorhabditis elegans as a model of human disease. Trends Biotechnol 20(4):147-8
126. Miyasaka T et al (2005) Progressive neurodegeneration in C. Elegans model of tauopathy. Neurobiol Dis 20(2):372-83
127. Fatouros C et al (2012) Inhibition of tau aggregation in a novel Caenorhabditis elegans model of tauopathy mitigates proteotoxicity. Hum Mol Genet 21(16):3587-603
128. McCormick, A.V.; et al.; Dopamine D2 receptor antagonism suppresses tau aggregation and neurotoxicity. Biol Psychiatry, 2012
129. Guthrie CR, Schellenberg GD, Kraemer BC (2009) SUT-2 potentiates tau-induced neurotoxicity in Caenorhabditis elegans. Hum Mol Genet 18(10):1825-38
130. Kraemer BC, Schellenberg GD (2007) SUT-1 enables tau-induced neurotoxicity in C. Elegans. Hum Mol Genet 16(16):1959-71
131. Barr MM, Sternberg PW (1999) A polycystic kidney-disease gene homologue required for male mating behaviour in C. Elegans. Nature 401(6751):386-9
132. Igarashi P, Somlo S (2002) Genetics and pathogenesis of polycystic kidney disease. J Am Soc Nephrol 13(9):2384-98
133. Lee JE, Gleeson JG (2011) Cilia in the nervous system: linking cilia function and neurodevelopmental disorders. Curr Opin Neurol 24(2):98-105
134. Hirose S et al (2005) Genetics of idiopathic epilepsies. Epilepsia 46(Suppl 1):38-43
135. Lu Y, Wang X (2009) Genes associated with idiopathic epilepsies: a current overview. Neurol Res 31(2):135-43
136. Noebels JL (2003) Exploring new gene discoveries in idiopathic generalized epilepsy. Epilepsia 44(Suppl 2):16-21
137. Kash SF et al (1997) Epilepsy in mice deficient in the 65-kDa isoform of glutamic acid decarboxylase. Proc Natl Acad Sci USA 94(25):14060-5
138. Kearney JA et al (2006) Severe epilepsy resulting from genetic interaction between Scn2a and Kcnq2. Hum Mol Genet 15(6):1043-8
139. Noebels JL, Sidman RL (1979) Inherited epilepsy: spike-wave and focal motor seizures in the mutant mouse tottering. Science 204(4399):1334-6
140. Smart SL et al (1998) Deletion of the K(V)1.1 potassium channel causes epilepsy in mice. Neuron 20(4):809-19
141. Zhang X et al (2010) Deletion of the potassium channel Kv12.2 causes hippocampal hyperexcitability and epilepsy. Nat Neurosci 13(9):1056-8
142. Khosravani H, Zamponi GW (2006) Voltage-gated calcium channels and idiopathic generalized epilepsies. Physiol Rev 86(3):941-66
143. Williams SN et al (2004) Epileptic-like convulsions associated with LIS-1 in the cytoskeletal control of neurotransmitter signaling in Caenorhabditis elegans. Hum Mol Genet 13(18):2043-59
144. Nehrke K, Denton J, Mowrey W (2008) Intestinal Ca2+ wave dynamics in freely moving C. Elegans coordinate execution of a rhythmic motor program. Am J Physiol Cell Physiol 294(1):C333-44
145. Stawicki TM et al (2011) TRPM channels modulate epileptic-like convulsions via systemic ion homeostasis. Curr Biol 21(10):883-8
146. Steinlein OK et al (1995) A missense mutation in the neuronal nicotinic acetylcholine receptor alpha 4 subunit is associated with autosomal dominant nocturnal frontal lobe epilepsy. Nat Genet 11(2):201-3
147. Monteilh-Zoller MK et al (2003) TRPM7 provides an ion channel mechanism for cellular entry of trace metal ions. J Gen Physiol 121(1):49-60
148. Hsiao B, Dweck D, Luetje CW (2001) Subunit-dependent modulation of neuronal nicotinic receptors by zinc. J Neurosci 21(6):1848-56
149. Smart TG, Hosie AM, Miller PS (2004) Zn2+ ions: modulators of excitatory and inhibitory synaptic activity. Neuroscientist 10(5):432-42
150. Pandey R et al (2010) Baccoside A suppresses epileptic-like seizure/convulsion in Caenorhabditis elegans. Seizure 19(7):439-442
151. Dibbens LM et al (2009) Familial and sporadic 15q13.3 microdeletions in idiopathic generalized epilepsy: precedent for disorders with complex inheritance. Hum Mol Genet 18(19):3626-3631
152. Helbig I et al (2009) 15q13.3 microdeletions increase risk of idiopathic generalized epilepsy. Nat Genet 41(2):160-162
153. Steinlein OK, Bertrand D (2008) Neuronal nicotinic acetylcholine receptors: from the genetic analysis to neurological diseases. Biochem Pharmacol 76(10):1175-1183
154. Brown LA et al (2006) Contributions from Caenorhabditis elegans functional genetics to antiparasitic drug target identification and validation: Nicotinic acetylcholine receptors, a case study. Int J Parasitol 36(6):617-624
155. Ballivet M et al (1996) Nicotinic acetylcholine receptors in the nematode Caenorhabditis elegans. J Mol Biol 258(2):261-269
156. Mongan NP et al (1998) An extensive and diverse gene family of nicotinic acetylcholine receptor alpha subunits in Caenorhabditis elegans. Recept Channels 6(3):213-228
157. Francis MM et al (2005) The Ror receptor tyrosine kinase CAM-1 is required for ACR-16-mediated synaptic transmission at the C. Elegans neuromuscular junction. Neuron 46(4):581-594
158. Farias GG et al (2007) Wnt-7a induces presynaptic colocalization of alpha 7-nicotinic acetylcholine receptors and adenomatous polyposis coli in hippocampal neurons. J Neurosci 27(20):5313-25
159. Jensen M et al (2012) Wnt signaling regulates acetylcholine receptor translocation and synaptic plasticity in the adult nervous system. Cell 149(1):173-87
160. Pevsner J, Hsu SC, Scheller RH (1994) n-Sec1: a neural-specific syntaxin-binding protein. Proc Natl Acad Sci U S A 91(4):1445-1449
161. Hamdan FF et al (2009) De novo STXBP1 mutations in mental retardation and nonsyndromic epilepsy. Ann Neurol 65(6):748-753
162. Gengyo-Ando K et al (1993) The C. Elegans unc-18 gene encodes a protein expressed in motor neurons. Neuron 11(4):703-711
163. Weimer RM et al (2003) Defects in synaptic vesicle docking in unc-18 mutants. Nat Neurosci 6(10):1023-1030
164. McEwen JM, Kaplan JM (2008) UNC-18 promotes both the anterograde trafficking and synaptic function of syntaxin. Mol Biol Cell 19(9):3836-3846
165. Wu MN et al (1999) Syntaxin 1A interacts with multiple exocytic proteins to regulate neurotransmitter release in vivo. Neuron 23(3):593-605
166. Gerber SH et al (2008) Conformational switch of syntaxin-1 controls synaptic vesicle fusion. Science (New York, NY) 321(5895):1507-1510
167. Verhage M et al (2000) Synaptic assembly of the brain in the absence of neurotransmitter secretion. Science 287(5454):864-869
168. Dobyns WB et al (1993) Lissencephaly. A human brain malformation associated with deletion of the LIS1 gene located at chromosome 17p13. JAMA 270(23):2838-42
169. Kitamura K et al (2002) Mutation of ARX causes abnormal development of forebrain and testes in mice and X-linked lissencephaly with abnormal genitalia in humans. Nat Genet 32(3):359-69
170. Kumar RA et al (2010) TUBA1A mutations cause wide spectrum lissencephaly (smooth brain) and suggest that multiple neuronal migration pathways converge on alpha tubulins. Hum Mol Genet 19(14):2817-2827
171. Pilz DT et al (1998) LIS1 and XLIS (DCX) mutations cause most classical lissencephaly, but different patterns of malformation. Hum Mol Genet 7(13):2029-37
172. Sossey-Alaoui K et al (1998) Human doublecortin (DCX) and the homologous gene in mouse encode a putative Ca2 + -dependent signaling protein which is mutated in human X-linked neuronal migration defects. Hum Mol Genet 7(8):1327-32
173. Jaglin XH, Chelly J (2009) Tubulin-related cortical dysgeneses: microtubule dysfunction underlying neuronal migration defects. Trends Genet 25(12):555-66
174. Hong SE et al (2000) Autosomal recessive lissencephaly with cerebellar hypoplasia is associated with human RELN mutations. Nat Genet 26(1):93-6
175. Locke CJ et al (2006) Genetic interactions among cortical malformation genes that influence susceptibility to convulsions in C. Elegans. Brain Res 1120(1):23-34
176. Locke CJ et al (2009) Pharmacogenetic analysis reveals a post-developmental role for Rac GTPases in Caenorhabditis elegans GABAergic neurotransmission. Genetics 183(4):1357-1372
177. Evason K et al (2008) Valproic acid extends Caenorhabditis elegans lifespan. Aging Cell 7(3):305-17
178. Evason K et al (2005) Anticonvulsant medications extend worm life-span. Science 307(5707):258-62
179. Forthun RB et al (2012) Cross-species functional genomic analysis identifies resistance genes of the histone deacetylase inhibitor valproic acid. PLoS One 7(11):e48992
180. Palcoux JB, Niaudet P, Goumy P (1994) Side effects of levamisole in children with nephrosis. Pediatr Nephrol 8(2):263-4
181. Joly C et al (1998) Acute levamisole poisoning. Presse Med 27(15):717
182. Jamain S et al (2003) Mutations of the X-linked genes encoding neuroligins NLGN3 and NLGN4 are associated with autism. Nat Genet 34(1):27-9
183. Laumonnier F et al (2004) X-linked mental retardation and autism are associated with a mutation in the NLGN4 gene, a member of the neuroligin family. Am J Hum Genet 74(3):552-7
184. Yan J et al (2008) Analysis of the neuroligin 4Y gene in patients with autism. Psychiatr Genet 18(4):204-7
185. Sato D et al (2012) SHANK1 deletions in males with autism spectrum disorder. Am J Hum Genet 90(5):879-87
186. Kim HG et al (2008) Disruption of neurexin 1 associated with autism spectrum disorder. Am J Hum Genet 82(1):199-207
187. Calahorro F, Ruiz-Rubio M (2011) Caenorhabditis elegans as an experimental tool for the study of complex neurological diseases: Parkinson's disease, Alzheimer's disease and autism spectrum disorder. Invertebr Neurosci 11(2):73-83
188. Calahorro F, Ruiz-Rubio M (2012) Functional phenotypic rescue of Caenorhabditis elegans neuroligin-deficient mutants by the human and rat NLGN1 genes. PLoS One 7(6):e39277-e39277
189. Calahorro, F.; E. Alejandre, and M. Ruiz-Rubio, Osmotic avoidance in Caenorhabditis elegans: synaptic function of two genes, orthologues of human NRXN1 and NLGN1, as candidates for autism. J Vis Exp, 2009(34)
190. Hunter JW et al (2010) Neuroligin-deficient mutants of C. Elegans have sensory processing deficits and are hypersensitive to oxidative stress and mercury toxicity. Dis Model Mech 3(5-6):366-376
191. Filipek PA et al (2000) Practice parameter: screening and diagnosis of autism: report of the Quality Standards Subcommittee of the American Academy of Neurology and the Child Neurology Society. Neurology 55(4):468-79
192. Chauhan A, Chauhan V (2006) Oxidative stress in autism. Pathophysiology 13(3):171-81
193. Haklai-Topper L et al (2011) The neurexin superfamily of Caenorhabditis elegans. Gene Expr Patterns 11(1-2):144-50
194. Naisbitt S et al (1999) Shank, a novel family of postsynaptic density proteins that binds to the NMDA receptor/PSD-95/GKAP complex and cortactin. Neuron 23(3):569-82
195. Sala C et al (2001) Regulation of dendritic spine morphology and synaptic function by Shank and Homer. Neuron 31(1):115-30
196. Sala C et al (2005) Key role of the postsynaptic density scaffold proteins Shank and Homer in the functional architecture of Ca2+ homeostasis at dendritic spines in hippocampal neurons. J Neurosci 25(18):4587-92
197. Jee C et al (2004) SHN-1, a Shank homologue in C. Elegans, affects defecation rhythm via the inositol-1,4,5-trisphosphate receptor. FEBS Lett 561(1-3):29-36
198. Oh WC et al (2011) ANK repeat-domain of SHN-1 Is indispensable for in vivo SHN-1 function in C. Elegans. Mol Cells 31(1):79-84
199. Hung AY et al (2008) Smaller dendritic spines, weaker synaptic transmission, but enhanced spatial learning in mice lacking Shank1. J Neurosci 28(7):1697-708
200. Castermans D et al (2003) The neurobeachin gene is disrupted by a translocation in a patient with idiopathic autism. J Med Genet 40(5):352-6
201. Wang X et al (2000) Neurobeachin: a protein kinase A-anchoring, beige/Chediak-higashi protein homolog implicated in neuronal membrane traffic. J Neurosci 20(23):8551-65
202. Medrihan L et al (2009) Neurobeachin, a protein implicated in membrane protein traffic and autism, is required for the formation and functioning of central synapses. J Physiol 587(Pt 21):5095-106
203. Volders K, Nuytens K, Creemers JW (2011) The autism candidate gene Neurobeachin encodes a scaffolding protein implicated in membrane trafficking and signaling. Curr Mol Med 11(3):204-17
204. de Souza N et al (2007) SEL-2, the C. Elegans neurobeachin/LRBA homolog, is a negative regulator of lin-12/Notch activity and affects endosomal traffic in polarized epithelial cells. Development 134(4):691-702
205. Shamloula HK et al (2002) rugose (rg), a Drosophila A kinase anchor protein, is required for retinal pattern formation and interacts genetically with multiple signaling pathways. Genetics 161(2):693-710
206. Katidou M et al (2008) The immunoglobulin superfamily of neuronal cell adhesion molecules: lessons from animal models and correlation with human disease. Biotechnol J 3(12):1564-80
207. Rosenthal A, Jouet M, Kenwrick S (1992) Aberrant splicing of neural cell adhesion molecule L1 mRNA in a family with X-linked hydrocephalus. Nat Genet 2(2):107-12
208. Jouet M et al (1993) A missense mutation confirms the L1 defect in X-linked hydrocephalus (HSAS). Nat Genet 4(4):331
209. Fransen E et al (1995) CRASH syndrome: clinical spectrum of corpus callosum hypoplasia, retardation, adducted thumbs, spastic paraparesis and hydrocephalus due to mutations in one single gene, L1. Eur J Hum Genet 3(5):273-84
210. Marui T et al (2009) Association of the neuronal cell adhesion molecule (NRCAM) gene variants with autism. Int J Neuropsychopharmacol 12(1):1-10
211. Zallen JA, Kirch SA, Bargmann CI (1999) Genes required for axon pathfinding and extension in the C. Elegans nerve ring. Development 126(16):3679-92
212. Wang X et al (2005) A role for the C. Elegans L1CAM homologue lad-1/sax-7 in maintaining tissue attachment. Dev Biol 284(2):273-91
213. Sasakura H et al (2005) Maintenance of neuronal positions in organized ganglia by SAX-7, a Caenorhabditis elegans homologue of L1. EMBO J 24(7):1477-88
214. Pocock R et al (2008) Functional dissection of the C. Elegans cell adhesion molecule SAX-7, a homologue of human L1. Mol Cell Neurosci 37(1):56-68
215. Wang X et al (2008) The C. Elegans L1CAM homologue LAD-2 functions as a coreceptor in MAB-20/Sema2 mediated axon guidance. J Cell Biol 180(1):233-46
216. Castellani V et al (2000) Analysis of the L1-deficient mouse phenotype reveals cross-talk between Sema3A and L1 signaling pathways in axonal guidance. Neuron 27(2):237-49
217. Falk J et al (2005) Dual functional activity of semaphorin 3B is required for positioning the anterior commissure. Neuron 48(1):63-75
218. Wright AG et al (2007) Close homolog of L1 and neuropilin 1 mediate guidance of thalamocortical axons at the ventral telencephalon. J Neurosci 27(50):13667-79
219. Demyanenko GP, Shibata Y, Maness PF (2001) Altered distribution of dopaminergic neurons in the brain of L1 null mice. Brain Res Dev Brain Res 126(1):21-30
220. Demyanenko GP et al (2004) Close homolog of L1 modulates area-specific neuronal positioning and dendrite orientation in the cerebral cortex. Neuron 44(3):423-37
221. Demyanenko GP et al (2011) NrCAM deletion causes topographic mistargeting of thalamocortical axons to the visual cortex and disrupts visual acuity. J Neurosci 31(4):1545-58
222. Macosko EZ et al (2009) A hub-and-spoke circuit drives pheromone attraction and social behaviour in C. Elegans. Nature 458(7242):1171-1175
223. Wu Q et al (2003) Developmental control of foraging and social behavior by the Drosophila neuropeptide Y-like system. Neuron 39(1):147-61
224. Karl T et al (2010) Schizophrenia-relevant behaviours in a genetic mouse model for Y2 deficiency. Behav Brain Res 207(2):434-40
225. Ramanathan S et al (2004) A case of autism with an interstitial deletion on 4q leading to hemizygosity for genes encoding for glutamine and glycine neurotransmitter receptor sub-units (AMPA 2, GLRA3, GLRB) and neuropeptide receptors NPY1R, NPY5R. BMC Med Genet 5:10
226. Kramer JM, van Bokhoven H (2009) Genetic and epigenetic defects in mental retardation. Int J Biochem Cell Biol 41(1):96-107
227. Bond J et al (2002) ASPM is a major determinant of cerebral cortical size. Nat Genet 32(2):316-320
228. Higgins J et al (2010) Human ASPM participates in spindle organisation, spindle orientation and cytokinesis. BMC Cell Biol 11:85-85
229. van der Voet M et al (2009) NuMA-related LIN-5, ASPM-1, calmodulin and dynein promote meiotic spindle rotation independently of cortical LIN-5/GPR/Galpha. Nat Cell Biol 11(3):269-277
230. Galli M et al (2011) aPKC phosphorylates NuMA-related LIN-5 to position the mitotic spindle during asymmetric division. Nat Cell Biol 13(9):1132-1138
231. Fraser AG et al (2000) Functional genomic analysis of C. Elegans chromosome I by systematic RNA interference. Nature 408(6810):325-330
232. Simmer F et al (2003) Genome-wide RNAi of C. Elegans using the hypersensitive rrf-3 strain reveals novel gene functions. PLoS Biol 1(1):E12-E12
233. Piano F et al (2002) Gene clustering based on RNAi phenotypes of ovary-enriched genes in C. Elegans. Curr Biol 12(22):1959-1964
234. Pulvers JN et al (2010) Mutations in mouse Aspm (abnormal spindle-like microcephaly associated) cause not only microcephaly but also major defects in the germline. Proc Natl Acad Sci U S A 107(38):16595-16600
235. Laumonnier F et al (2005) Mutations in PHF8 are associated with X linked mental retardation and cleft lip/cleft palate. J Med Genet 42(10):780-786
236. Koivisto AM et al (2007) Screening of mutations in the PHF8 gene and identification of a novel mutation in a Finnish family with XLMR and cleft lip/cleft palate. Clin Genet 72(2):145-149
237. Qiu J et al (2010) The X-linked mental retardation gene PHF8 is a histone demethylase involved in neuronal differentiation. Cell Res 20(8):908-918
238. Kleine-Kohlbrecher D et al (2010) A functional link between the histone demethylase PHF8 and the transcription factor ZNF711 in X-linked mental retardation. Mol Cell 38(2-2):165-178
239. Stromme P et al (2002) Mutations in the human ortholog of Aristaless cause X-linked mental retardation and epilepsy. Nat Genet 30(4):441-5
240. Melkman T, Sengupta P (2005) Regulation of chemosensory and GABAergic motor neuron development by the C. Elegans Aristaless/Arx homolog alr-1. Development 132(8):1935-49
241. Poirier K et al (2007) Large spectrum of lissencephaly and pachygyria phenotypes resulting from de novo missense mutations in tubulin alpha 1A (TUBA1A). Hum Mutat 28(11):1055-64
242. Baran R et al (2010) Motor neuron synapse and axon defects in a C. Elegans alpha-tubulin mutant. PLoS One 5(3):e9655
243. Epstein CJ (2006) Down's syndrome: critical genes in a critical region. Nature 441(7093):582-583
244. Guipponi M et al (2000) C21orf5, a novel human chromosome 21 gene, has a Caenorhabditis elegans ortholog (pad-1) required for embryonic patterning. Genomics 68(1):30-40
245. Rachidi M et al (2007) New cerebellar phenotypes in YAC transgenic mouse in vivo library of human Down syndrome critical region-1. Biochem Biophys Res Commun 364(3):488-94
246. Rachidi M, Lopes C (2008) Mental retardation and associated neurological dysfunctions in Down syndrome: a consequence of dysregulation in critical chromosome 21 genes and associated molecular pathways. Eur J Paediatr Neurol EJPN Off J Eur Paediatr Neurol Soc 12(3):168-182
247. Arron JR et al (2006) NFAT dysregulation by increased dosage of DSCR1 and DYRK1A on chromosome 21. Nature 441(7093):595-600
248. Dierssen M, de Lagrån MMN (2006) DYRK1A (dual-specificity tyrosine-phosphorylated and -regulated kinase 1A): a gene with dosage effect during development and neurogenesis. Sci World J 6:1911-1922
249. Park J, Song W-J, Chung K (2009) Function and regulation of Dyrk1A: towards understanding Down syndrome. Cell Mol Life Sci 66(20):3235-3240
250. Raich WB et al (2003) Characterization of Caenorhabditis elegans homologs of the Down syndrome candidate gene DYRK1A. Genetics 163(2):571-580
251. Altafaj, X.; et al.; Normalization of Dyrk1A expression by AAV2/1-shDyrk1A attenuates hippocampal-dependent defects in the Ts65Dn mouse model of Down syndrome. Neurobiol Dis, 2012
252. Guedj F et al (2009) Green tea polyphenols rescue of brain defects induced by overexpression of DYRK1A. PLoS One 4(2):e4606
253. Ortiz-Abalia J et al (2008) Targeting Dyrk1A with AAVshRNA attenuates motor alterations in TgDyrk1A, a mouse model of Down syndrome. Am J Hum Genet 83(4):479-88
254. Strippoli P et al (2000) A new gene family including DSCR1 (Down syndrome candidate region 1) and ZAKI-4: characterization from yeast to human and identification of DSCR1-like 2, a novel human member (DSCR1L2). Genomics 64(3):252-263
255. Fuentes JJ et al (2000) DSCR1, overexpressed in Down syndrome, is an inhibitor of calcineurin-mediated signaling pathways. Hum Mol Genet 9(11):1681-1690
256. Groth RD, Dunbar RL, Mermelstein PG (2003) Calcineurin regulation of neuronal plasticity. Biochem Biophys Res Commun 311(4):1159-1171
257. Nguyen T, Di Giovanni S (2008) NFAT signaling in neural development and axon growth. Int J Dev Neurosci Off J Int Soc Dev Neurosci 26(2):141-145
258. Lee JI et al (2003) The Caenorhabditis elegans homologue of Down syndrome critical region 1, RCN-1, inhibits multiple functions of the phosphatase calcineurin. J Mol Biol 328(1):147-156
259. Kalscheuer VM et al (2003) Mutations in the polyglutamine binding protein 1 gene cause X-linked mental retardation. Nat Genet 35(4):313-315
260. Lenski C et al (2004) Novel truncating mutations in the polyglutamine tract binding protein 1 gene (PQBP1) cause Renpenning syndrome and X-linked mental retardation in another family with microcephaly. Am J Hum Genet 74(4):777-780
261. Lubs H et al (2006) Golabi-to-Hall syndrome results from a missense mutation in the WW domain of the PQBP1 gene. J Med Genet 43(6):e30-e30
262. Takahashi, K.; et al.; Nematode homologue of PQBP1, a mental retardation causative gene, is involved in lipid metabolism. PLoS One, 2009. 4(1)
263. Gibbons RJ et al (1995) Mutations in a putative global transcriptional regulator cause X-linked mental retardation with alpha-thalassemia (ATR-X syndrome). Cell 80(6):837-845
264. Gibbons R (2006) Alpha thalassaemia-mental retardation, X linked. Orphanet J Rare Dis 1:15-15
265. Picketts DJ et al (1996) ATRX encodes a novel member of the SNF2 family of proteins: mutations point to a common mechanism underlying the ATR-X syndrome. Hum Mol Genet 5(12):1899-1907
266. Kernohan KD et al (2010) ATRX partners with cohesin and MeCP2 and contributes to developmental silencing of imprinted genes in the brain. Dev Cell 18(2):191-202
267. Bender AM, Wells O, Fay DS (2004) lin-35/Rb and xnp-1/ATR-X function redundantly to control somatic gonad development in C. Elegans. Dev Biol 273(2):335-349
268. Cardoso C et al (2005) XNP-1/ATR-X acts with RB, HP1 and the NuRD complex during larval development in C. Elegans. Dev Biol 278(1):49-59
269. Chubb JE et al (2008) The DISC locus in psychiatric illness. Mol Psychiatry 13(1):36-64
270. Soares DC et al (2011) DISC1: structure, function, and therapeutic potential for major mental illness. ACS Chem Neurosci 2(11):609-632
271. Chen S-Y, Huang P-H, Cheng H-J (2011) Disrupted-in-schizophrenia 1-mediated axon guidance involves TRIO-RAC-PAK small GTPase pathway signaling. Proc Natl Acad Sci U S A 108(14):5861-5866
272. Briancon-Marjollet A et al (2008) Trio mediates netrin-1-induced Rac1 activation in axon outgrowth and guidance. Mol Cell Biol 28(7):2314-23
273. Kwok TC et al (2006) A small-molecule screen in C. Elegans yields a new calcium channel antagonist. Nature 441(7089):91-5
274. Calamini B et al (2012) Small-molecule proteostasis regulators for protein conformational diseases. Nat Chem Biol 8(2):185-96
275. Wormbase. Available from: http://www.wormbase.org.
276. Rijkers K et al (2010) Polymorphisms in CACNA1E and Camk2d are associated with seizure susceptibility of Sprague-Dawley rats. Epilepsy Res 91(1):28-34
277. Genetics home reference. Available from: http://ghr.nlm.nih.gov/gene/
278. Liu Q, Hollopeter G, Jorgensen EM (2009) Graded synaptic transmission at the Caenorhabditis elegans neuromuscular junction. Proc Natl Acad Sci USA 106(26):10823-8
279. Thorgeirsson TE et al (2008) A variant associated with nicotine dependence, lung cancer and peripheral arterial disease. Nature 452(7187):638-42
280. Saitsu H et al (2008) De novo mutations in the gene encoding STXBP1 (MUNC18-1) cause early infantile epileptic encephalopathy. Nat Genet 40(6):782-8
281. Bellanger JM et al (2012) The doublecortin-related gene zyg-8 is a microtubule organizer in Caenorhabditis elegans neurons. J Cell Sci 125(Pt 22):5417-27
282. Gonczy P et al (2001) zyg-8, a gene required for spindle positioning in C. Elegans, encodes a doublecortin-related kinase that promotes microtubule assembly. Dev Cell 1(3):363-75
283. Ackman JB et al (2009) Abnormal network activity in a targeted genetic model of human double cortex. J Neurosci 29(2):313-27
284. Kerjan G et al (2009) Mice lacking doublecortin and doublecortin-like kinase 2 display altered hippocampal neuronal maturation and spontaneous seizures. Proc Natl Acad Sci USA 106(16):6766-71
285. Alkuraya FS et al (2011) Human mutations in NDE1 cause extreme microcephaly with lissencephaly [corrected]. Am J Hum Genet 88(5):536-47
286. Willemsen MH et al (2012) Mutations in DYNC1H1 cause severe intellectual disability with neuronal migration defects. J Med Genet 49(3):179-83
287. Fu AK et al (2005) Aberrant motor axon projection, acetylcholine receptor clustering, and neurotransmission in cyclin-dependent kinase 5 null mice. Proc Natl Acad Sci USA 102(42):15224-9
288. Chae T et al (1997) Mice lacking p35, a neuronal specific activator of Cdk5, display cortical lamination defects, seizures, and adult lethality. Neuron 18(1):29-42
289. Topalidou I, van Oudenaarden A, Chalfie M (2011) Caenorhabditis elegans aristaless/Arx gene alr-1 restricts variable gene expression. Proc Natl Acad Sci U S A 108(10):4063-4068
290. Tucker M et al (2005) The Caenorhabditis elegans aristaless orthologue, alr-1, is required for maintaining the functional and structural integrity of the amphid sensory organs. Mol Biol Cell 16(10):4695-4704
291. Gloria-Soria A, Azevedo RBR (2008) npr-1 regulates foraging and dispersal strategies in Caenorhabditis elegans. Curr Biol 18(21):1694-1699
292. Rogers C et al (2003) Inhibition of Caenorhabditis elegans social feeding by FMRFamide-related peptide activation of NPR-1. Nat Neurosci 6(11):1178-1185
293. Asada H et al (1996) Mice lacking the 65 kDa isoform of glutamic acid decarboxylase (GAD65) maintain normal levels of GAD67 and GABA in their brains but are susceptible to seizures. Biochem Biophys Res Commun 229(3):891-5
294. Kulkarni SJ, Newby LM, Jackson FR (1994) Drosophila GABAergic systems. II. Mutational analysis of chromosomal segment 64AB, a region containing the glutamic acid decarboxylase gene. Mol Gen Genet 243(5):555-64
295. Cossette P et al (2002) Mutation of GABRA1 in an autosomal dominant form of juvenile myoclonic epilepsy. Nat Genet 31(2):184-9
296. DeLorey TM et al (1998) Mice lacking the beta3 subunit of the GABAA receptor have the epilepsy phenotype and many of the behavioral characteristics of Angelman syndrome. J Neurosci 18(20):8505-14
297. Schuler V et al (2001) Epilepsy, hyperalgesia, impaired memory, and loss of pre- and postsynaptic GABA(B) responses in mice lacking GABA(B(1)). Neuron 31(1):47-58
298. Lee D, Su H, O'Dowd DK (2003) GABA receptors containing Rdl subunits mediate fast inhibitory synaptic transmission in Drosophila neurons. J Neurosci 23(11):4625-34