Free-living flatworms under the knife: Past and present

Development Genes and Evolution

Volumn 217, Issue 2, 2007, Pages 89-104

  Egger, Bernhard ^a   Gschwentner, Robert ^a   Rieger, Reinhard ^a  

^a UNIVERSITY OF INNSBRUCK   (Austria)

Author keywords

Acoela; Catenulida; Planarian; Platyhelminthes; Rhabditophora

Indexed keywords

ASEXUAL REPRODUCTION; BRAIN DEVELOPMENT; BRAIN FUNCTION; DEVELOPMENTAL STAGE; EMBRYO DEVELOPMENT; EMBRYO PATTERN FORMATION; EVOLUTIONARY DEVELOPMENTAL BIOLOGY; GENE EXPRESSION REGULATION; NONHUMAN; PHYLOGENY; PLATYHELMINTH; PRIORITY JOURNAL; REGENERATION; REPRODUCTION; REVIEW; RNA INTERFERENCE; SEASONAL VARIATION; SENSE ORGAN; SEX DIFFERENCE; SPECIES DIFFERENCE; STARVATION; TAXONOMY; TOTIPOTENT STEM CELL;

ANIMALS; BRAIN; FEMALE; MALE; NERVOUS SYSTEM PHYSIOLOGY; OVARY; PLATYHELMINTHS; REGENERATION; REPRODUCTION; SPECIES SPECIFICITY; TOTIPOTENT STEM CELLS; TURBELLARIA;

ACOELA; ANIMALIA; CATENULIDA; MACROSTOMORPHA; MACROSTOMUM LIGNANO; PLANARIA; PLATYHELMINTHES; TRICLADIDA;

EID: 33846817337     PISSN: 0949944X     EISSN: None     Source Type: Journal    
DOI: 10.1007/s00427-006-0120-5     Document Type: Review

References (137)

1. Åkesson B, Gschwentner R, Hendelberg J, Ladurner P, Müller H, Rieger R (2001) Fission in Convolutriloba longifissura: Asexual reproduction in acoelous turbellarians revisited. Acta Zool (Stockh) 82:231-239
2. Agata K (2003) Regeneration and gene regulation in planarians. Curr Opin Genet Dev 13:492-496
3. Agata K, Watanabe K (1999) Molecular and cellular aspects of planarian regeneration. Semin Cell Dev Biol 10:377-383
4. Agata K, Tanaka T, Kobayashi C, Kato K, Saitoh Y (2003) Intercalary regeneration in planarians. Dev Dyn 226:308-316
5. Ax P, Schulz E (1959) Ungeschlechtliche Fortpflanzung durch Paratomie bei acoelen Turbellarien. Biol Zentralbl 78:613-622
6. Baguñà J (1998) Planarians. In: Ferretti P, Géraudie J (eds) Cellular and molecular basis of regeneration: from invertebrates to humans. Wiley, pp 135-165
7. Baguñà J, Riutort M (2004a) Molecular phylogeny of the Platyhelminthes. Can J Zool 82:168-193
8. Baguñà J, Riutort M (2004b) The dawn of bilaterian animals: The case of acoelomorph flatworms. Bioessays 26:1046-1057
9. Baguñà J, Saló E, Auladell C (1989) Regeneration and pattern formation in planarians - III. Evidence that neoblasts are totipotent stem cells and the source of blastema cells. Development 107:77-86
10. Boyer BC (1986) Determinative development in the polyclad turbellarian, Hoploplana inquilina. Int J Invertebr Reprod Dev 9:243-251
11. Boyer BC (1989) The role of the first quartet micromeres in the development of the polyclad Hoploplana inquilina. Biol Bull 177:338-343
12. Boyer BC (1992) The effect of deleting opposite first quartet micromeres on the development of the polyclad Hoploplana. Biol Bull 183:374-375
13. Brøndsted HV (1939) Regeneration in planarians investigated with a new transplantation technique. K Dan Vidensk Selsk Biol Meddr 15:1-39
14. Brøndsted HV (1942) Further experiments on regeneration - problems in planarians. K Dan Vidensk Selsk Biol Meddr 17:1-27
15. Brøndsted HV (1969) Planarian regeneration. Pergamon Press, Oxford
16. Cardona A, Hartenstein V, Romero R (2005) The embryonic development of the triclad Schmidtea polychroa. Dev Genes Evol 215:109-131
17. Cebrià F, Newmark PA (2005) Planarian homologs of netrin and netrin receptor are required for proper regeneration of the central nervous system and the maintenance of nervous system architecture. Development 132:3691-3703
18. Cebrià F, Kudome T, Nakazawa M, Mineta K, Ikeo K, Gojobor T, Agata K (2002a) The expression of neural-specific genes reveals the structural and molecular complexity of the planarian central nervous system. Mech Dev 116:199-204
19. Cebrià F, Kobayashi C, Umesono Y, Nakazawa M, Mineta K, Ikeo K, Gojobori T, Itoh M, Taira M, Sánchez Alvarado A, Agata K (2002b) FGFR-related gene nou-darake restricts brain tissues to the head region of planarians. Nature 419:620-624
20. Child CM (1903a) Studies on regulation. I. Fission and regulation in Stenostoma. Arch Entwm 15:187-237, 355-420
21. Child CM (1903b) Studies on regulation. II. Experimental control of form-regulation in zooids and pieces of Stenostoma. Arch Entwm 15:603-637
22. Child CM (1904a) Studies on regulation. IV. Some experimental modifications of form-regulation in Leptoplana. J Exp Zool 1:95-133
23. Child CM (1904b) Studies on regulation. V. The relation between the central nervous system and regeneration in Leptoplana: Posterior regeneration. J Exp Zool 1:463-512
24. Child CM (1904c) Studies on regulation. VI. The relation between the central nervous system and regulation in Leptoplana: Anterior and lateral regeneration. J Exp Zool 1:513-557
25. Child CM (1905a) Studies on regulation. VII. Further experiments on form-regulation in Leptoplana. J Exp Zool 2:253-285
26. Child CM (1905b) Studies on regulation. VIII. Functional regulation and regeneration in Cestoplana. Arch Entwm 19:261-294
27. Child CM (1905c) Studies on regulation. X. The positions and proportions of parts during regulation in Cestoplana in the absance of the cephalic ganglia. Arch Entwm 20:157-186
28. Child CM (1907) The localisation of different methods of form-regulation in Polychoerus caudatus. Arch Entwm Org 23:227-248
29. Dalyell JG (1814) Observations on some interesting phenomena in animal physiology exhibited by several species of planariae. Edinburgh
30. Egger B, Ishida S (2005) Chromosome fission or duplication in Macrostomum lignano (Macrostomorpha, Plathelminthes) - remarks on chromosome numbers in "archoophoran turbellarians". J Zool Syst Evol Res 43:127-132
31. Egger B, Salvenmoser W, Nimeth K, Adamski Z, Ladurner P, Rieger R (2005) Role and dynamics of stem cells during regeneration in the flatworm Macrostomum lignano. Folia Histochem Cytobiol 43 (Suppl 1):40
32. Egger B, Ladurner P, Nimeth K, Gschwentner R, Rieger R (2006a) The regeneration capacity of the flatworm Macrostomum lignano - on repeated regeneration, rejuvenation, and the minimal size needed for regeneration. Dev Genes Evol 216:565-577
33. Egger B, Ladurner P, Nimeth K, Gschwentner R, Rieger R (2006b) The regeneration capacity of the flatworm Macrostomum lignano - on repeated regeneration, rejuvenation, and the minimal size needed for regeneration. Dev Genes Evol 216:579-580
34. Ehlers U (1985) Das phylogenetische System der Plathelminthes. Fischer, Jena
35. Faisst J, Keenan CL, Loopowitz H (1980) Neuronal repair and avoidance behavior in the flatworm Notoplana acticola. J Neurobiol 11:483-496
36. Fulinski B (1922) Über das Restitutionsvermögen der Rhabdocoelen. Arch Entwm 51:575-586
37. Ghirardelli E (1965) Differentiation of the germ cell and regeneration of the gonads in planarians. In: Regeneration in animals. Amsterdam, pp 177-184
38. Giesa S (1966) Die Embryonalentwicklung von Monocelis fusca Oersted. Z Morphol Ökol Tiere 57:137-230
39. Goss RJ (1991) The natural history (and mystery) of regeneration. In: Dinsmore CE (ed) A history of regeneration research: Milestones in the evolution of science. Cambridge University Press, Cambridge
40. Gremigni V (1992) Features of sex evolution in Platyhelminthes-Turbellaria. In: Dallai R (ed) Sex origin and evolution. Selected symposia and monographs U Z I, vol 6. Mucchi, Modena, pp. 69-86
41. Hagleithner G (1946) Das Regenerations problem bei Turbellarien. Dissertation, Innsbruck
42. Hanson ED (1967) Regeneration in acoelous flatworms: The role of the peripheral parenchyma. Roux' Arch Entwm 159:298-313
43. Haranghy L, Balázs A (1964) Ageing and rejuvenation in planarians. Exp Gerontol 1:77-91
44. Hein C (1928) Zur Kenntnis der Regnerationsvorgänge bei den Rhabdocoelen. Mit Angaben über den feineren Bau und die Lebensäußerungen. Z Wiss Zool 130:469-546
45. Hendelberg J, Åkesson B (1988) Convolutriloba retrogemma gen. et sp.n., a turbellarian (Acoela, Platyhelminthes) with reversed polarity of reproductive buds. Fortschr Zool 36:321-327
46. Hendelberg J, Åkesson B. (1991) Studies of the budding process in Convolutriloba retrogemma (Acoela, Platyhelminthes). Hydrobiologia 227:11-17
47. Henley C (1974) Platyhelminthes (Turbellaria). In: Giese AC, Pearse JS (eds) Reproduction of marine invertebrates, vol 1. Acoelomate and pseudocoelomate metazoans. Academic, New York, pp 267-343
48. Hyman LH (1951) The Invertebrates. II. Platyhelminthes and Rhynchocoela. The acoelomate Bilateria. McGraw-Hill, New York
49. Ishida S (1998) Regeneration in the polyclads. In: Teshirogi W, Watanabe K (eds) Morpho-differentiation in planarians. Kyoritsu Shuppan Company, Tokyo, pp 223-240
50. Jondelius U (2004) Cleavage in Nemertoderma westbladi (Nemertodermatida) and its phylogenetic significance. Zoomorphology 123:221-225
51. Keil EM (1929) Regeneration in Polychoerus caudatus Mark. Biol Bull 57:225-244
52. Keller J (1894) Die ungeschlechtliche Fortpflanzung der Süßwasserturbellarien. Jena Z Med Naturwiss 28:370-407
53. Koinuma S, Umesono Y, Watanabe K, Agata K (2003) The expression of planarian brain factor homologs, DjFoxG and DjFoxD. Gene Exp Pat 3:21-27
54. Koopowitz H, Silver D, Rose G (1975) Neuronal plasticity and recovery of function in a polyclad flatworm. Nature 256:737-738
55. Koopowitz H, Silver D, Rose G (1976) Primitive nervous systems. Control and recovery of feeding behavior in the polyclad flatworm, Notoplana acticola. Biol Bull 150:411-425
56. Kreshchenko N, Sheiman I, Reuter M, Gustafsson MKS, Halton DW, Maule AG (2001) Effects of FMRFamide-related peptides and neuropeptides F on planarian regeneration (Platyhelminhtes, Tricladida). Belg J Zool 131:147-148
57. Ladurner P, Mair GR, Reiter D, Salvenmoser W, Rieger RM (1997) Serotonergic nervous system of two macrostomid species: Recent or ancient divergence? Invertebr Biol 116:178-191
58. Ladurner P, Rieger R, Baguñà J (2000) Spatial distribution and differentiation potential of stem cells in hatchlings and adults in the marine platyhelminth Macrostomum sp.: A bromodeoxyuridine analysis. Dev Biol 226:231-241
59. Le Moigne A (1966) Etude du développement embryonnaire et recherches sur les cellules de régénération chez l'embryon de la Planaire Polycelis nigra (Turbellarié, Triclade). J Embryol Exp Morphol 15:39-60
60. Lender TH (1950) Démonstration du role organisateur du cerveau dans la régénération des yeux de la planaire Polycelis nigra par la méthode des greffes. C R Soc Biol 144:1407
61. Lender TH (1951a) Découverte d'une plainaire américaine, Dugesia (Euplanaria) tigrina. Girard Ass Philom d'Alsace et de Lorraine 9:51
62. Lender TH (1951b) Sur les propriétés et l'étendue du champ d'organisation du cervau dans la régénération des yeux de la planaire Polycelis nigra. C r Séanc Soc Biol 145:1211
63. Lender TH (1951c) Sur les capacités inductrices de l'organisateur des yeux dans la régénération de la planaire Polycelis nigra (Ehr.): Action du cerveau en voie de dégénérescence et en greffes hétéroplastiques. C r Séanc Soc Biol 145:1378
64. Lus J (1924) Studies on regeneration and transplantation in Turbellaria. I. Some considerations on polarity and heteromorphosis in fresh water planarians. Bull Soc Nat Mosc Sect Biol, Exp 1
65. Monti R (1900a) La rigenerazione nelle planarie marine. Mem R Ist Lomb 19:1-16
66. Monti R (1900b) Studi sperimentali sulla rigenerazione nei Rhabdoceli marini (Plagiostoma girardii-Graff). Rend Ist Lomb Sci Lett Ser II 33:915-917
67. Moraczewski J (1977) Asexual reproduction and regeneration of Catenula (Turbellaria, Archoophora). Zoomorphologie 88:65-80
68. Morgan TH (1902) Growth and regeneration in Planaria lugubris. Arch Entwm 13:179-212
69. Morgan LV (1905) Incomplete anterior regeneration in the absence of the brain in Leptoplana littoralis. Biol Bull 9:187-193
70. Morris J, Nallur R, Ladurner P, Egger B, Rieger R, Hartenstein V (2004) The embryonic development of the flatworm Macrostomum sp. Dev Genes Evol 214:220-239
71. Newmark PA, Sánchez Alvarado A (2001) Regeneration in planaria. Encyclopedia of Life Sciences, Nature Publishing Group, London, 1-7
72. Newmark PA, Sánchez Alvarado A (2002) Not your father's planarian: A classic model enters the era of functional genomics. Nat Rev Genet 3:210-220
73. Nimeth KT, Mahlknecht M, Mezzanato A, Peter R, Rieger R, Ladurner P (2004) Stem cell dynamics during growth, feeding, and starvation in the basal flatworm Macrostomum sp. (Platyhelminthes). Dev Dyn 230:91-99
74. Olmsted JMD (1922a) The role of the nervous system in the regeneration of polyclad Turbellaria. J Exp Zool 36:48-56
75. Olmsted JMD (1922b) The role of the nervous system in the locomotion of certain marine polyclads. J Exp Zool 36:57-66
76. Pallas PS (1774) Spicilegia zoologica quibus novae imprimis et obscurae animaliu. speciosiconibus atque conamentariis illustratur. Fasc X, Berolini
77. Palmberg I (1986) Cell migration and differentiation during wound healing and regeneration in Microstomum lineare (Turbellaria). Hydrobiologia 132:181-188
78. Palmberg I (1990) Stem cells in microturbellarians - an autoradiographic and immunocytochemical study. Protoplasma 158:109-120
79. Palmberg I (1991) Differentiation during asexual reproduction and regeneration in a microturbellarian. Hydrobiologia 227:1-10
80. Pechlaner R (1957) Die Regenerationsfähigkeit von Otomesostoma auditivum (Forel et Duplessis) (Turbellaria). Arch Entwm 150:104-114
81. Peebles F (1913) Regeneration acoeler Plattẅrmer. I. Aphanostoma diversicolor. Bull Inst Océanogr 263:1-5
82. Peter R, Ladurner P, Rieger RM (2001) The role of stem cell strategies in coping with environmental stress and choosing between alternative reproductive modes: Turbellaria rely on a single cell type to maintain individual life and propagate species. Mar Ecol 22:35-51
83. Pfister D, Ladurner P (2005) The totipotent stem cell system as a source for germ line cells during development and regeneration in the flatworm Macrostomum lignano. Dev Biol 283: 643
84. Ramachandra NB, Gates RD, Ladurner P, Jacobs DK, Hartenstein V (2002) Embryonic development in the primitive bilaterian Neochildia fusca: normal morphogenesis and isolation of POU genes Brn-1 and Brn-3. Dev Genes Evol 212:55-69
85. Randolph H (1897) Observations and experiments on regeneration in planarians. Arch Entwm 5:352-3725
86. Rand HW, Mildred E (1926) Inhibition of regeneration in two-headed or two-tailed planarians. Proc Natl Acad Sci 12:570-574
87. Reddien PW, Sánchez Alvarado A (2004) Fundamentals of planarian regeneration. Annu Rev Cell Dev Biol 20:725-757
88. Reddien PW, Bermange AL, Murfitt KJ, Jennings JR, Sánchez Alvarado A (2005) Identification of genes needed for regeneration, stem cell function, and tissue homeostasis by systematic gene perturbation in planaria. Dev Cell 8:635-649
89. Reuter M, Kreshchenko N (2004) Flatworm asexual multiplication implicates stem cells and regeneration. Can J Zool 82:334-356
90. Reuter M, Raikova OI, Jondelius U, Gustafsson MKS, Maule AG, Halton DW (2001) Organisation of the nervous system in the Acoela: An immunocytochemical study. Tissue Cell 33:119-128
91. Rieger R (1986) Asexual reproduction and the turbellarian archetype. Hydrobiologia 132:35-45
92. Rieger R (1996) Plathelminthes, Plattwürmer. In: Westheide W, Rieger R (eds) Spezielle Zoologie I. Einzeller und Wirbellose Tiere. Gustav Fischer Verlag, Stuttgart, pp 210-258
93. Rieger RM, Legniti A, Ladurner P, Reiter D, Asch E, Salvenmoser W, Schürmann W, Peter R (1999) Ultrastructure of neoblasts in microturbellaria: Significance for understanding stem cells in free-living Platyhelminthes. Invertebr Reprod Dev 35:127-140
94. Ritter WE, Congdon EM (1900) On the inhibition by artificial section of the normal fission plane in Stenostoma. Proc Calif Acad Sci 3(2):365-377
95. Ruhl L (1927a) Regenerationserscheinungen an Rhabdocoelen. Zool Anz 72:160-175
96. Ruhl L (1927b) Doppelbildungen und andere Mißbildungen bei Stenostomum. Zool Anz 72:180-190
97. Saló E (2006) The power of regeneration and the stem-cell kingdom: Freshwater planarians (Platyhelminthes). Bioessays 28:546-559
98. Saló E, Baguñà J (2002) Regeneration in planarians and other worms: New findings, new tools, and new perspectives. J Exp Zool 292:528-539
99. Salvenmoser W, Riedl D, Ladurner P, Rieger R (2001) Early steps in the regeneration of the musculature in Macrostomum sp. (Macrostomorpha). Belg J Zool 131 (Suppl 1):105-109
100. Sánchez Alvarado A (2000) Regeneration in the metazoans: Why does it happen? Bioessays 22:578-590
101. Sánchez Alvarado A (2003) The freshwater planarian Schmidtea mediterranea: Embryogenesis, stem cells and regeneration. Curr Opin Genet Dev 13:438-444
102. Sánchez Alvarado A (2004) Regeneration and the need for simpler model organisms. Phil Trans R Soc Lond B 359:759-763
103. Sánchez Alvarado A (2006) Planarian regeneration: Its end is its beginning. Cell 124:241-245
104. Sánchez Alvarado A, Kang H (2005) Multicellularity, stem cells, and the neoblasts of the planarian Schmidtea mediterranea. Exp Cell Res 306:299-308
105. Scharer L, Joss G, Sandner P (2004) Mating behaviour of the marine turbellarian Macrostomum sp.: These worms suck. Mar Biol 145:373-380
106. Schultz E (1901) Über Regeneration bei Polycladen. Zool Anz 24:527-529
107. Schultz E (1902) Aus dem Gebiete der Regeneration. II. Über die Regeneration der Turbellarien. Z Wiss Zool 72:1-30
108. Seilern-Aspang F (1958) Entwicklungsgeschichtliche Studien an paludicolen Tricladen. Arch Entwm 150:425-480
109. Sekera E (1911) Weitere Beitráge zu den Doppelbildungen bei den Turbellarien. Ber Ges Wiss Prag Math-naturwiss Kl III:1-7
110. Shibata N, Umesono Y, Orii H, Sakurai T, Watanabe K, Agata K (1999) Expression of vasa (vas)-related genes in germline cells and totipotent somatic stem cells in planarians. Dev Biol 206:73-87
111. Ŝivickis PB (1930) A quantitative study of regeneration along the main axis of the triclad body. Arch Zool Ital 16:430-449
112. Smith JPS, Tyler S, Rieger RM (1986) Is the Turbellaria polyphyletic? Hydrobiologia 132:13-21
113. Steinböck O (1927) Monographie der Prorhynchidae (Turbellaria). Z Morphol Ökol Tiere 8:538-662
114. Steinböck O (1954) Sobre la misión del "plasmodio digestivo" en la regeneracion de Amphiscolops (Turbellaria acoela). Publ Inst Biol Apl (Barcelona) 17:101-117
115. Steinböck O (1955) Regeneration azöler Turbellarien. Zool Anz (Suppl Bd) 18:86-94
116. Steinböck O (1963a) Regenerations- und Konplantationsversuche an Amphiscolops sp. (Turbellaria acoela). Arch Entwm Org 154:308-353
117. Steinböck O (1963b) Regeneration experiments and phylogeny. Comp Biol Phylog 8:108-112
118. Steinböck O (1966) Die Hofsteniiden (Turbellaria acoela): Grundsätzliches zur Evolution der Turbellarien. Z Zoolog Syst Evolforsch 4:58-195
119. Steinböck O (1967) Regenerationsversuche mit Hofstenia giselae Steinb. (Turbellaria Acoela). Arch Entwm 158:394-458
120. Steinmann P, Bresslau E (1913) Die Strudelwürmer (Turbellaria). In: Ziegler HE, Woltereck R (eds) Monographien einheimischer Tiere, Band 5. Klinkhardt Verlag, Leipzig
121. Stevens NM, Boring AM (1905) Regeneration in Polychoerus caudatus. J Exp Zool 2:335-346
122. Teshirogi W, Ishida S, Yamazaki H (1977) Regenerative capacities of transverse pieces in the two species of freshwater planarian, Dendrocoelopsis lactea and Polycelis sapporo. Sci Rep Hirosaki Univ 24:55-72
123. Toledo A, Cruz C, Fragoso G, Laclette JP, Merchant MT, Hernandez M, Sciutto E (1997) In vitro culture of Taenia crassiceps larval cells and cyst regeneration after injection into mice. J Parasitol 83:189-193
124. Török LJ (1958) Experimental contributions to the regenerative capacity of Dugesia (= Euplanaria) lugubris, O Schm. Acta Biol 9:79
125. Tyler S, Hooge M (2004) Comparative morphology of the body wall in flatworms (Platyhelminthes). Can J Zool 82:194-210
126. Tyler S, Schilling S, Hooge M, Bush LF (comp) (2006) Turbellarian taxonomic database. Version 1.5 http://www.turbellaria.umaine.edu/
127. van Cleave CD (1929) An experimental study of fission and reconstitution in Stenostomum. Physiol Zool 2:18-58
128. von Graff L (1882) Monographie der Turbellarien. I. Rhabdocoelida. Leipzig
129. von Graff L (1908) Acoela und Rhabdoelida. In: Bronn HG (ed) Klassen und Ordnungen des Tierreichs. Vierter Band: Vermes. I. c. Turbellaria. Akad Verl-Ges Geest u Portig, Leipzig
130. von Levetzow KG (1939) Die Regeneration der polycladen Turbellarien. Arch Entwm 139:780-818
131. Vannini E (1965) Regeneration and sex gradient in some hermaphroditic animals. In: Regeneration in animals. Amsterdam, pp 160-176
132. Vannini E (1966) Alcune aspette attuali dei probleme della rigenerazione. Arch Zool Ital 51:951-958
133. Wolff E, Lender TH (1950a) Sur le déterminisme de la régénération des yeux chez une planaire d'eau douce Polycelis nigra. C r Séanc Soc Biol 144:1213
134. Wolff E, Lender TH (1950b) Sur le role organisateur du cerveau dans la régénération des yeux chez une planaire d'eau douce. C r Acad Sci 230:2238-2239
135. Yamasu T (1991) Fine structure and function of ocelli and sagittocysts of acoel flatworms. Hydrobiologia 227:273-282
136. Younossi-Hartenstein A, Hartenstein V (2000) The embryonic development of the polyclad flatworm Imogine mcgrathi. Dev Genes Evol 210:383-398
137. Younossi-Hartenstein A, Hartenstein V (2001) The embryonic development of the temnocephalid flatworms Craspedella pedum and Diceratocephala boschmai. Cell Tissue Res 304:295-310