Molecular mechanisms of holoprosencephaly

Molecular Genetics and Metabolism

Volumn 68, Issue 2, 1999, Pages 126-138

  Wallis, Deeann E ^a   Muenke, Maximilian ^a,b  

^a UNIVERSITY OF PENNSYLVANIA   (United States)

^b NATIONAL HUMAN GENOME RESEARCH INSTITUTE   (United States)

Author keywords

Forebrain development; Holoprosencephaly; Nodal; One eyed pinhead; SIX3; Sonic Hedgehog; TGIF; ZIC2

Indexed keywords

CONGENITAL MALFORMATION; FOREBRAIN; GENE TARGETING; HOLOPROSENCEPHALY; MODEL; MOLECULAR GENETICS; PRIORITY JOURNAL; SHORT SURVEY;

CUBITUS; ERINACEIDAE; VERTEBRATA;

EID: 0032759342     PISSN: 10967192     EISSN: None     Source Type: Journal    
DOI: 10.1006/mgme.1999.2895     Document Type: Article

References (132)

1. Matsunaga E, Shiota K. Holoprosencephaly in human embryos: Epidemiologic studies of 150 cases. Terat. 16:1977;261-272.
2. Roach E, DeMyer W, Conneally P M, Palmer C, Merritt A D. Holoprosencephaly: Birth data, genetic and demographic analysis of 30 families. Birth Defects: Original Article Series. 11:1975;294-313.
3. Muenke M. Clinical, cytogenetic, and molecular approaches to the genetic heterogeneity of holoprosencephaly. Am J Med Genet. 34:1989;237-245.
4. Cohen M M Jr. Perspectives on holoprosencephaly: Part I. Terat. 40:1989;211-235.
5. Muenke M. Holoprosencephaly as a genetic model for normal craniofacial development. Dev Biol. 5:1994;293-301.
6. Roessler E, Muenke M. Holoprosencephaly: A paradigm for the complex genetics of brain development. J Inher Metab Dis. 21:1998;481-497.
7. Croen L A, Shaw G M, Lammer E J. Holoprosencephaly: Epidemiologic and clinical characteristics of a California population. Am J Med Genet. 64:1996;465-472.
8. Cohen M M Jr. Perspectives on holoprosencephaly: Part III. Spectra, distinctions, continuities, and discontinuities. Am J Med Genet. 34:1989;271-288.
9. Ming J E, Muenke M. Holoprosencephaly: From Homer to Hedgehog. Clin Genet. 53:1998;155-163.
10. Golden J A. Holoprosencephaly: A defect in brain patterning. J Neuropathol Exp Neurol. 57:1998;991-999.
11. Norman M G, McGillivray B C, Kalousek D K, Hill A, Poskitt K J. Holoprosencephaly: Defects of the mediobasal prosencephalon. Congenital Malformations of the Brain: Pathological, Embryological, Clinical, Radiological and Genetic Aspects. 1995;Oxford Univ Press, New York. p. 187-221.
12. DeMyer W E, Zeman W. Alobar holoprosencephaly (arhinencephaly) with median cleft lip and palate: Clinical, electroencephalographic and nosologic considerations. Confin Neurol. 23:1963;1-36.
13. DeMyer W, Zeman W, Palmer C G. The face predicts the brain: diagnostic significance of median facial anomalies for holoprosencephaly (arhinencephaly). Pediatrics. 34:1964;256-263.
14. Lammer E, Chen D, Hoar R, Agnish N, Benke P, Braun J, Curry C, Fernhoff P, Grix A, Lott I, Richards J, Sun S. Retinoic acid embryopathy. N Eng J Med. 313:1985;837-841.
15. Nanni, L, Ming, J, E, Bocian, M, Steinhaus, K, Bianchi, D, W, Die-Smulders, C, Giannotti, A, Imaizumi, K, Jones, K, L, Campo, M, D, Martin, R, A, Meinecke, P, Pierpont, M, EM, Robin, N, H, Young, I, D, Roessler, E, Muenke, M, The mutational spectrum of the Sonic hedgehog gene in holoprosencephaly: SHH mutations cause a significant proportion of autosomal dominant holoprosencephaly, Hum Mol Genet, [in press], 1999.
16. Brown S A, Warburton D, Brown L Y, Yu C-y, Roeder E R, Stengel-Rutkowski S, Hennekam R CM, Muenke M. Holoprosencephaly due to mutations in ZIC2, a homologue of Drosophila odd-paired. Nature Genet. 20:1998;180-183.
17. Müller F, O'Rahilly R. Mediobasal prosencephalic defects, including holoprosencephaly and cyclopia, in relation to the development of the human forebrain. Am J Anat. 185:1989;391-414.
18. Spemann H, Mangold H. Über Induktion von Embryonalanlagen durch Implantation artfremder Organisatoren. Arch Mikr Anat Entwicklungsmech. 100:1924;599-638.
19. Wolpert, L, Beddington, R, Brockes, J, Jessell, T, Lawrence, P, Meyerowitz, E, Principles of Development, New York, Oxford Univ Press.
20. Nüsslein-Volhard C, Wieschaus E. Mutations affecting segment number and polarity in Drosophila. Nature. 287:1980;795-801.
21. Marigo V, Roberts D J, Lee S MK, Tsukurov O, Levi T, Gastier J M, Epstein D J, Gilbert D J, Copeland N G, Seidman C E, Jenkins N A, Seidman J G, McMahon A P, Tabin C. Cloning, expression, and chromosomal location of SHH and IHH: Two human homologs of the Drosophila segment polarity gene hedgehog. Genomics. 28:1995;44-51.
22. Ming J E, Roessler E, Muenke M. Human developmental disorders and the Sonic hedgehog pathway. Mol Med Today. 8:1998;343-349.
23. Roelink H, Augsburger A, Heemskerk J, Korzh V, Norlin S, Ruiz i Altaba A, Tanabe Y, Placzek M, Edlund T, Jessell T M, Dodd J. Floorplate and motorneuron induction by vhh-1, a vertebrate homolog of hedgehog expressed by the notocord. Cell. 76:1994;761-775.
24. Chiang C, Litingtung Y, Lee E, Young K E, Corden J L, Westphal H, Beachy P A. Cyclopia and defective axial patterning in mice lacking Sonic hedgehog gene function. Nature. 383:1994;407-413.
25. Gurrieri F, Trask, BJ, Engh Gvd, Krauss C M, Schinzel A, Pettenati M J, Schindler D, Dietz-Band J, Vergnaud G, Scherer S W, Tsui L-C, Muenke M. Physical mapping of the holoprosencephaly minimal critical region on chromosome 7q36. Nature Genet. 3:1993;247-251.
26. Muenke M, Gurrieri F, Bay C, Yi D H, Collins A L, Johnson V P, Hennekam R CM, Schaefer G B, Weik L, Lubinski M S, Daack-Hirsch S, Moore C A, Dobyns W B, Murray J C, Price R A. Linkage of a human brain malformation, familial holoprosencephaly, to chromosome 7 and evidence for genetic heterogeneity. Proc Natl Acad Sci USA. 91:1994;8102-8106.
27. Belloni E, Muenke M, Roessler E, Traverso G, Siegel-Bartelt J, Frumkin A, Mitchell H F, Donis-Keller H, Helms C, Hing A V, Heng H HQ, Koop B, Martindale D, Rommens J M, Tsui L-C, Scherer S W. Identification of Sonic hedgehog as a candidate gene responsible for holoprosencephaly. Nature Genet. 14:1996;353-356.
28. Roessler E, Belloni E, Gaudenz K, Jay P, Berta P, Scherer S W, Tsui L-C, Muenke M. Mutations in the human Sonic hedgehog gene cause holoprosencephaly. Nature Genet. 14:1996;357-360.
29. Roessler E, Belloni E, Gaudenz K, Vargus F, Scherer S W, Tsui L-C, Muenke M. Mutations in the C-terminal domain of Sonic hedgehog cause holoprosencephaly. Hum Mol Genet. 6:1997;1847-1853.
30. Roessler E, Ward D E, Gaudenz K, Belloni E, Scherer S W, Donnai D, Siegel-Bartelt J, Tsui L-C, Muenke M. Cytogeneic rearrangements involving the loss of the Sonic hedgehog gene at 7q36 cause holoprosencephaly. Hum Genet. 100:1997;172-181.
31. Lee J J, Ekker S C, Kessler D Pv, Porter J A, Sun B I, Beachy P A. Autoproteolysis in hedgehog protein biogenesis. Science. 266:1994;1528-1537.
32. Porter J A, Young K E, Beachy P A. Cholesterol modification of hedgehog signaling proteins in animal development. Science. 274:1996;255-259.
33. Porter J A, Ekker S C, Park W-J, Kessler D Pv, Young K E, Chen C-H, Ma Y, Woods A S, Cotter R J, Koonin E V, Beachy P A. Hedgehog patterning activity: Role of lipophilic modification mediated by the carboxy-terminal autoprocessing domain. Cell. 86:1996;21-34.
34. Kelley R I, Roessler E, Hennekam R CM, Feldman G L, Kosaki K, Jones M C, Palumbos J C, Muenke M. Holoprosencephaly in RSH/Smith-Lemli-Opitz Syndrome: Does abnormal cholesterol metabolism affect the function of Sonic Hedgehog. Am J Med Genet. 66:1996;478-484.
35. Waterham H R, Wijburg F A, Hennekam R C, Vreken P, Poll-The B T, Dorland L, Duran M, Jira P E, Smeitink J A, Wevers R A, Wanders R J. Smith-Lemli-Opitz syndrome is caused by mutations in the 7-dehydrocholesterol reductase gene. Am J Hum Genet. 63:1998;329-338.
36. Wassif C A, Maslen C, Kachilele-Linjewile S, Lin D, Linck L M, Connor W E, Steiner R D, Porter F D. Mutations in the human sterol delta7-reductase gene at 11q12-13 cause Smith-Lemli-Optiz syndrome. Am J Hum Genet. 63:1998;55-62.
37. Fitzky B U, Witsch-Baumgartner M, Erdel M, Lee J N, Paik Y K, Glossmann H, Utermann G, Moebius F F. Mutations in the delta1-sterol reductase gene in patients with the Smith-Lemli-Opitz syndrome. Proc Natl Acad Sci USA. 95:1998;8181-8186.
38. Reppeto M, Maziere J C, Citadelle D, Dupuis R, Meier M, Biade S, Quiec D, Roux C. Teratogenic effect of the cholesterol synthesis inhibitor AY 9944 on rat embryos in vitro. Terat. 42:1990;611-618.
39. Roux C, Horvath C, Dupuis R. Teratogenic action and embryo lethality of AY 9944. Prevention of a hypercholesterolemia-provoking diet. Terat. 19:1979;35-38.
40. Lanoue L, Dehart D B, Hinsdale M E, Maeda N, Tint G S, Sulik K K. Limb, genital, CNS, and facial malformations result from gene/environment-induced cholesterol deficiency: Further evidence for a link to Sonic Hedgehog. Am J Med Genet. 73:1997;24-31.
41. Cooper M K, Porter J A, Young K E, Beachy P A. Teratogen-mediated inhibition of target tissue response to Shh signaling. Science. 280:1998;1603-1607.
42. Willnow T E, Hilpert J, Armstrong S A, Rholmann A, Hammer R E, Burns D K, Herz J. Defective forebrain development in mice lacking gp330/megalin. Proc Natl Acad Sci USA. 93:1996;8460-8464.
43. Johnson R L, Scott M P. New players and puzzles in the Hedgehog signaling pathway. Curr Opin Genet Dev. 8:1998;450-456.
44. Tabin C J, McMahon A P. Recent advances in hedgehog signaling. Trends Cell Biol. 7:1997;442-446.
45. Stone D M, Hynes M, Armanini M, Swanson T A, Gu Q, Johnson R L, Scott M P, Pennica D, Goddard A, Phillips H, Noll M, Hooper J E, Sauvage Fd, Rosenthal A. The tumor-suppressor gene patched encodes a candidate receptor for Sonic hedgehog. Nature. 384:1996;129-134.
46. Marigo V, Davey R A, Zuo Y, Cunningham J M, Tabin C J. Biochemical evidence that patched is the hedgehog receptor. Nature. 384:1996;176-179.
47. Goodrich L V, Johnson R L, Milenkovic L, McMahon J A, Scott M P. Conservation of the hedgehog/patched signaling pathway from flies to mice: induction of a mouse patched gene by hedgehog. Genes Dev. 10:1996;301-312.
48. Ming J E, Kaupas M E, Roessler E, Brunner H G, Nance W E, Stratton R F, Sujansky E, Bale S J, Muenke M. Mutations of PATCHED in holoprosencephaly. Am J Hum Genet. 63:1998;A27.
49. Heuvel Mvd, Ingham P W. smoothened encodes a receptor-like serpentine protein required for hedgehog signaling. Nature. 382:1996;547-551.
50. Alcedo J, Ayzenzon M, Ohlen T V, Noll M, Hooper J E. The Drosophila smoothened gene encodes a seven-pass membrane protein, a putative receptor for the hedgehog signal. Cell. 86:1996;221-232.
51. Chuang P-T, McMahon A P. Vertebrate Hedgehog signalling modulated by induction of a Hedgehog-binding protein. Nature. 397:1999;617-621.
52. Alexandre C, Jacinto A, Ingham P W. Transcriptional activation of hedgehog target genes in Drosophila is mediated directly by the Cubitus interruptus protein, a member of the GLI family of zinc finger DNA-binding proteins. Genes Dev. 10:1996;2003-2013.
53. Orenic T, Chidsey J, Holmgreen R. Cell and cubitus interruptus Dominant: Two segment polarity genes on the fourth chromosome in Drosophila. Dev Biol. 124:1987;50-56.
54. Hui C-c, Slusarski D, Platt K A, Holmgreen R, Joyner A L. Expression of three mouse homologs of the Drosophila segment polarity gene cubitus interuptus. Gli, Gli-2, and Gli-3, in ectoderm and mesoderm-derived tissues suggests multiple roles during postimplantation development. Dev Biol. 162:1994;402-413.
55. Lee J, Platt K A, Censullo P, Ruiz i Altaba A. Gli1 is a target of Sonic hedgehog that induces ventral neural tube development. Development. 124:1997;2537-2552.
56. Ruiz i Altaba A. Catching a Gli-mpse of Hedgehog. Cell. 90:1997;193-196.
57. Hynes M, Stone D M, Dowd M, Pitts-Meek S, Goddard A, Gurney A, Rosenthal A. Control of cell pattern in the neural tube by the zinc finger transcription factor and oncogene Gli-1. Neuron. 19:1997;15-26.
58. Hardcastle Z, Mo R, Hui C-c, Sharpe P T. The Shh pathway in tooth development: Defects in Gli2 and Gli3 mutants. Development. 125:1998;2803-2811.
59. Biesecker L G. Strike three for GLI3. Nature Genet. 17:1997;259-260.
60. Wild A, Kalff-Suske M, Vortkamp A, Bornholdt D, König R, Grzeschik K H. Point mutations in human GLI3 cause Greig syndrome. Hum Mol Genet. 6:1997;1979-1984.
61. Kang S, Graham J M Jr, Olney A H, Biesecker L G. GLI3 frameshift mutations cause autosomal dominant Pallister-Hall syndrome. Nature Genet. 15:1997;266-268.
62. Radhakrishna U, Wild A, Grzeschik K-H, Antonarakis S E. Mutation in GLI3 in postaxial polydactyly type A. Nature Genet. 17:1997;269-271.
63. Forbes, A, J, Nakano, Y, Taylor, A, M, Ingham, P, W. Genetic analysis of hedgehog signalling in the Drosophila embryo. Development (Suppl):115-124.
64. Tanabe Y, Jessell T M. Diversity and pattern in the developing spinal cord. Science. 274:1996;1115-1123.
65. Ikeya M, Lee S M, Johnson J E, McMahon A P, Takada S. Wnt signaling required for expansion of neural crest and CNS progenitors. Nature. 389:1997;966-970.
66. Yoshikawa Y, Fujimori T, McMahon A P, Takada S. Evidence that absence of Wnt-3a signaling promotes neuralization instead of paraxial mesoderm development in the mouse. Dev Biol. 183:1997;234-242.
67. Heberlein U, Wolff T, Rubin G M. The TGF beta homolog dpp and the segment polarity gene hedgehog are required for propagation of a morphogenetic wave in the Drosophila retina. Cell. 75:1993;913-926.
68. Hogan B LM. Bone morphogenetic proteins: Multifunctional regulators of vertebrate development. Genes Dev. 10:1996;1580-1594.
69. Furuta Y, Piston D W, Hogan B LM. Bone morphogenetic proteins (BMPs) as regulators of dorsal forebrain development. Development. 124:1997;2203-2212.
70. Golden J A, Bracilovic A, McFadden K A, Beesley J S, Rubenstein J LR, Grinspan J B. Ectopic bone morphogenetic proteins 5 and 4 in the chick forebrain lead to cyclopia and holoprosencephaly. Proc Natl Acad Sci USA. 96:1999;2439-2444.
71. Nagai T, Aruga J, Takada S, Gunther T, Sporle R, Schughart K, Mikoshiba K. The expression of the mouse Zic1, Zic2, and Zic3 gene suggests an essential role for Zic genes in body pattern formation. Dev Biol. 182:1997;299-313.
72. Aruga J, Nagai T, Tokuyama T, Hayashizaki Y, Okazaki Y, Chapman V M, Mikoshiba K. The mouse Zic Gene family: Homologues of the Drosophila pair-rule gene odd-paired. J Biol Chem. 271:1996;1043-1047.
73. Grinblat Y, Gamse J, Patel M, Sive H. Determination of the zebrafish forebrain: induction and patterning. Development. 125:1998;4403-4416.
74. Benedyk M J, Mullen J R, DiNardo S. odd-paired: A zinc finger pair-rule protein required for the timely activation of engrailed and wingless in Drosophila embryos. Genes Dev. 8:1994;105-117.
75. Cimbora D M, Sakonju S. Drosophila midgut morphogenesis requires the function of segmentation gene odd-paired. Dev Biol. 169:1995;580-595.
76. Brewster R, Lee J, Ruiz i Altaba A. Gli/Zic factors pattern the neural plate by defining domains of cell differentiation. Nature. 393:1998;579-583.
77. Schell U, Wienberg J, Kohler A, Bray-Ward P, Ward D E, Wilson W G, Allen W P, Lebel R R, Sawyer J R, Campbell P L, Aughton D J, Punnett H H, Lammer E J, Kao F-T, Ward D C, Muenke M. Molecular characterization of breakpoints in patients with holoprosencephaly and definition of the HPE2 critical region 2p21. Hum Mol Genet. 5:1996;223-229.
78. Wallis D E, Roessler E, Hehr U, Nanni L, Wiltshire T, Richiere-Costa A, Gillessen-Kaesbach G, Zackai E H, Rommens J, Muenke M. Mutations in the homeodomain of the human SIX3 gene cause holoprosencephaly. Nature Genet. 22:1999;196-198.
79. Oliver G, Mailhos A, Wehr R, Copeland N G, Jenkins N A, Gruss P. Six3, a murine homologue of the sine oculis gene, demarcates the most anterior border of the developing neural plate and is expressed during eye development. Development. 121:1995;4045-4055.
80. Oliver G, Loosli F, Koster R, Wittbrodt J, Gruss P. Ectopic lens induction in fish in response to the murine homeobox gene Six 3. Mech Dev. 60:1996;233-239.
81. Kobayashi M, Toyama R, Takada H, Dawid I B, Kawakami K. Overexpression of the forebrain-specific homeobox gene Six3 induces rostral forebrain enlargement in zebrafish. Development. 125:1998;2973-2982.
82. Loosli F, Winkler S, Wittbrodt J. Six3 overexpression initiates the formation of ectopic retina. Genes Dev. 13:1999;649-654.
83. Kawakami K, Ohto H, Takizawa T. Saito T. Identification and expression of sixfamily genes in mouse retina. FEBS Lett. 393:1996;259-263.
84. Cheyette B NR, Green P J, Martin K, Garren H, Hartenstein V, Zipursky S L. The Drosophila sine oculis locus encodes a homeodomain-containing protein required for the development of the entire visual system. Neuron. 12:1994;977-996.
85. Serikaku M A, O'Tousa J E. sine oculis is a homeobox gene required for Drosophila visual system development. Genetics. 138:1994;1137-1150.
86. Toy J, Yang J-M, Leppert G S, Sundin O H. The Optx2 homeobox gene is expressed in early precursors of the eye and activates retina-specific genes. Proc Natl Acad Sci USA. 95:1998;10643-10648.
87. Pignoni F, Hu B, Zavitz K H, Xiao J, Garrity P A, Zipursky S L. The eye-specification proteins So and Eya form a complex and regulate multiple steps in Drosophila eye development. Cell. 91:1997;881-891.
88. Chen R, Amoui M, Zhang Z, Mardon G. Dachshund and Eyes Absent proteins form a complex and function synergistically to induce ectopic eye development in Drosophila. Cell. 91:1997;893-903.
89. Chen R, Halder G, Zhang Z, Mardon G. Signaling by the TGF-β homolog decapentaplegic functions reiteratively within the network of genes controlling retinal cell fate determination in Drosophila. Development. 126:1999;935-943.
90. Halder G, Callaerts P, Flister S, Walldorf U, Kloter U, Gehring W J. Eyeless initiates the expression of both sine oculis and eyes absent during Drosophila compound eye development. Development. 125:1998;2181-2191.
91. Niimi T, Seimiya M, Kloter U, Flister S, Gehring W J. Direct regulatory interaction of the eyeless protein with an eye-specific enhancer in the sine oculis gene during eye induction in Drosophila. Development. 126:1999;2253-2260.
92. Kingsley D M. The TGF-β superfamily: New members, new receptors, and new genetic tests of function in different organisms. Genes Dev. 8:1994;133-146.
93. Heldin C-H, Miyazono K, Dijke Pt. TGF-β signalling from cell membrane to nucleus through SMAD proteins. Nature. 390:1997;465-471.
94. Whitman M. Smads and early developmental signaling by the TGFβ superfamily. Genes Dev. 12:1998;2445-2462.
95. Massague J. TGF-β signal transduction. Annu Rev Biochem. 67:1998;753-791.
96. Levin M, Mercola M. Evolutionary conservation of mechanisms upstream of asymmetric nodal expression: Reconciling chick and Xenopus. Dev Genet. 23:1998;185-193.
97. Conlon F L, Lyons K M, Takaesu N, Barth K S, Kispert A, Herrmann B, Robertson E J. A primary requirement for nodal in the formation and maintenance of the primitive streak in the mouse. Development. 120:1994;1919-1928.
98. Toyama R, O'Connell M L, Wright C VE, Kuehn M R, Dawid I B. Nodal induces ectopic goosecoid and lim1 expression and axis duplication in zebrafish. Development. 121:1995;383-391.
99. Nomura M, Li E. Smad2 role in mesoderm formation, left-right patterning and craniofacial development. Nature. 393:1998;786-790.
100. Rebagliati M R, Toyama R, Haffter P, Dawid I B. Cyclops encodes a nodal-related factor involved in midline signaling. Proc Natl Acad Sci USA. 95:1998;9932-9937.
101. Rebagliati M R, Toyama R, Fricke C, Haffter P, Dawid I B. Zebrafish nodal-related genes are implicated in axial patterning and establishing left-right asymmetry. Dev Biol. 199:1998;261-272.
102. Feldman B, Gates M A, Egan E S, Dougan S T, Rennebeck G, Sirotkin H I, Schier A F, Talbot W S. Zebrafish organizer development and germ-layer formation require nodal-related signals. Nature. 395:1998;181-185.
103. Hatta K, Kimmel C B, Ho R K, Walker C. The cyclops mutation blocks specification of the floor plate of the zebrafish nervous system. Nature. 350:1991;339-341.
104. Zhang J, Talbot W S, Schier A F. Positional cloning identifies zebrafish one-eyed pinhead as a permissive EGF-related ligand required during gastrulation. Cell. 92:1998;241-251.
105. Gritsman K, Zhang J, Cheng S, Heckscher E, Talbot W S, Schier A F. The EGF-CFC protein one-eyed pinhead is essential for nodal signaling. Cell. 97:1999;121-132.
106. Brand M, Heisenberg C-P, Warga R M, Pelegri F, Karlstrom R O, Beuchle D, Picker A, Jiang Y-J, Furutani-Seiki M, Eeden F JMv, Granato M, Haffter P, Hammerschmidt M, Kane D A, Kelsh R N, Mullins M C, Odenthal J, Nusslein-Volhard C. Mutations affecting development of the midline and general body shape during zebrafish embryogenesis. Development. 123:1996;129-142.
107. Schier A F, Neuhauss S CF, Helde K A, Talbot W S, Driever W. The one-eyed pinhead gene functions in mesoderm and endoderm formation in zebrafish and interacts with no tail. Development. 124:1997;327-342.
108. Wotton D, Lo R S, Lee S, Massague J. A Smad transcriptional corepressor. Cell. 97:1999;29-39.
109. Overhauser J, Mitchell H F, Zackai E H, Tick D B, Rojas K, Muenke M. Physical mapping of the holoprosencephaly critical region in 18p11.3. Am J Hum Genet. 57:1995;1080-1085.
110. Edwards M C, Liegeois N, Horecka J, DePinho R A, Sprague G F Jr., Tyers M, Elledge S J. Human CPR (Cell cycle progression restoration) genes impart a far-phenotype on yeast cells. Genetics. 147:1997;1063-1076.
111. Gripp K W, Edwards M C, Mowat D, Meinecke P, Richieri-Costa A, Zackai E H, Elledge S, Muenke M. Mutations in the transcription factor TGIF in holoprosencephaly. Am J Hum Genet. 63:1998;A32.
112. Bertolino E, Reimund B, Wildt-Perinic D, Clerc R G. A novel homeobox protein which recognizes a TGT core and functionally interferes with a retinoid-responsive motif. J Biol Chem. 270:1995;31178-31188.
113. Bertolino E, Wildt S, Richards G, Clerc R G. Expression of a novel murine homeobox gene in the developing cerebellar granular layer during its proliferation. Dev Dyn. 205:1996;410-420.
114. Webster W S, Johnston M C, Lammer E J, Sulik K. Isotretinoin embryopathy and the cranial neural crest: an in vivo and in vitro study. J Craniofac Genet. 6:1986;211-222.
115. Sulik K K, Cook C S, Webster W S. Teratogens and craniofacial malformations: relationships to cell death. Development. 103:1988;213-232.
116. Sulik K K, Dehart D B, Rogers J M, Chernoff N. Teratogenicity of low doses of all-trans retinoic acid in presomite mouse embryos. Terat. 51:1995;398-403.
117. Helms J A, Kim C H, Hu D, Minkoff R, Thaller C, Eichele G. Sonic hedgehog participates in craniofacial morphogenesis and is down-regulated by teratogenic doses of retinoic acid. Dev Biol. 187:1997;25-35.
118. Helms J A, Thaller C, Eichele G. Relationship between retinoic acid and sonic hedgehog, two polarizing signals in the chick wing bud. Development. 120:1994;3267-3274.
119. Oh S P, Li E. The signaling pathway mediated by the type IIB activin receptor controls axial patterning and lateral asymmetry in the mouse. Genes Dev. 11:1997;1812-1826.
120. Glinka A, Wu W, Delius H, Monaghan A P, Blumenstock C, Niehrs C. Dickkopf-1 is a member of a new family of secreted proteins and functions in head induction. Nature. 391:1998;357-362.
121. Ruiz i Altaba A, Prezioso V R, Darnell J E, Jessel T M. Sequential expression of HNF-3β and HNF-3α by embryonic organizing centers: the dorsal lip/node, notocord, and floor plate. Mech Dev. 44:1993;91-108.
122. Ang S-L, Rossant J. HNF-3β is essential for node and notochord formation in mouse development. Cell. 78:1994;561-574.
123. Weinstein D C, Ruiz i Altaba A, Chen W S, Hoodless P, Prezioso V R, Jessel T M, Darnell J E Jr. The winged-helix transcriptional factor HNF-3β is required for notochord development in the mouse embryo. Cell. 78:1994;575-588.
124. Sasaki H, Hui C-c, Nakafuku M, Kondoh H. A binding site for Gli proteins is essential for HNF-3β floor plate enhancer activity in transgenics and can respond to Shh in vitro. Development. 124:1997;1313-1322.
125. Filosa S, Rivera-Perez J A, Gomez A P, Gansmuller A, Sasaki H, Behringer R R, Ang S L. Goosecoid and HNF-3beta genetically interact to regulate neural tube patterning during mouse embryogenesis. Development. 124:1997;2843-2854.
126. Bouwmeester T, Kim S, Sasai Y, Lu B, De Robertis E M. Cerebrus is a head-inducing secreted factor expressed in the anterior endoderm of the Spemann organizer. Nature. 382:1996;595-601.
127. Piccolo S, Agius E, Leyns L, Bhattacharyya S, Grunz H, Bouwmeester T, De Robertis E M. The head inducer Cerebrus is a multifunctional antagonist of Nodal, BMP, and Wnt signals. Nature. 397:1999;707-710.
128. Talbot W S, Trevarrow B, Halpern M E, Melby A E, Farr G, Postlethwait J H, Jowett T, Kimmel C B, Kimelman D. A homeobox gene essential for zebrafish notocord development. Nature. 378:1995;150-157.
129. Halpern M E, Hatta K, Amacher S L, Talbot W S, Yan Y-L, Thisse B, Thisse C, Postlethwait J H, Kimmel C B. Genetic interactions in zebrafish midline development. Dev Biol. 187:1997;154-170.
130. Heisenberg C-P, Brand M, Jiang Y J, Warga R M, Beuchle D, Eeden F JMv, Furutani-Seiki M, Granato M, Haffter P, Hammerschmidt M, Kane D A, Kelsh R N, Mullins M C, Odenthal J, Nüsslein-Volhard C. Genes involved in forebrain development in the zebrafish, Danio rerio. Development. 123:1996;191-203.
131. Masai I, Heisenberg C P, Barth K A, Macdonald R, Adamek S, Wilson S W. floating head and masterblind regulate neuronal patterning in the roof of the forebrain. Neuron. 18:1997;43-57.
132. Fekany K, Yamanaka Y, Leung T, Sirotkin H I, Topczewski J, Gates M A, Hibi M, Renucci A, Stemple D, Radbill A, Schier A F, Dreiver W, Hirano T, Talbot W S, Solnica-Krezel L. The zebrafish bozozok locus encodes Dharma, a homeoprotein essential for induction of gastrula organizer and dorsoanterior embryonic structures. Development. 126:1999;1427-1438.