Evolution of Eye Regression in the Cavefish Astyanax: Apoptosis and the Pax-6 Gene'

SYNOPSIS. The eye is an extraordinary organ in terms of its development and evolution. In cave animals, the eye is sometimes reduced or eliminated as a consequence of adaptation to life in perpetual darkness. We have used the characid teleost Astyanax mexicanus as a model system to investigate the mechanisms of eye degeneration during the evolution of a cave vertebrate. Eyed surface populations of Astyanax entered caves during the Pleistocene, and their descendants lost their eyes and pigmentation. Astyanax populations exhibiting various degrees of eye regression have been reported in 29 Mexican caves. Surface populations with characteristics of the ancestral stock still exist in the vicinity of these caves. Thus, Astyanax represents one of the few instances in which the ancestral (surface fish) and the derived (cavefish) developmental modes are extant and available for comparative studies. The cavefish embryo develops an optic primordium consisting of a lens vesicle and optic cup but the rudimentary eye arrests in development and degenerates. Here we report that eye degeneration is accompanied by extensive apoptosis and downregulation of the Pax-6 gene in the developing lens. The results suggest that alterations in lens development are important factors in eye regression during cavefish evolution.

[1]  W. H. Lewis.  Experimental studies on the development of the eye in amphibia. II. On the cornea , 1905 .

[2]  C. R. Stockard.  The embryonic history of the lens in bdellostoma stouti in relation to recent experiments , 1906 .

[3]  C. Hubbs,et al.  The first known blind fish of the family Characidae: a new genus from Mexico , 1936 .

[4]  P. Cahn.  Comparative Optic Development in Astyanax Mexicanus and in Two of its Blind Cave Derivatives. , 1957 .

[5]  A. Coulombre.  EXPERIMENTAL EMBRYOLOGY OF THE VERTEBRATE EYE. , 1965, Investigative ophthalmology.

[6]  J. W. Saunders,et al.  Death in Embryonic Systems , 1966, Science.

[7]  J. Avise,et al.  EVOLUTIONARY GENETICS OF CAVE‐DWELLING FISHES OF THE GENUS ASTYANAX , 1972, Evolution; international journal of organic evolution.

[8]  J. Silver,et al.  The role of cell death during morphogenesis of the mammalian eye , 1973, Journal of morphology.

[9]  Ocular development and involution in the European cave salamander, Proteus anguinus laurenti. , 1976, The Biological bulletin.

[10]  R. Lande.  EVOLUTIONARY MECHANISMS OF LIMB LOSS IN TETRAPODS , 1978, Evolution; international journal of organic evolution.

[11]  E. Hay.  Development of the vertebrate cornea. , 1980, International review of cytology.

[12]  A. Wyllie,et al.  Cell death: the significance of apoptosis. , 1980, International review of cytology.

[13]  D. Culver.  Cave Life: Evolution and Ecology , 1982 .

[14]  M. Lyon,et al.  Small eyes (Sey): a homozygous lethal mutation on chromosome 2 which affects the differentiation of both lens and nasal placodes in the mouse. , 1986, Journal of embryology and experimental morphology.

[15]  L. Tsui,et al.  Genetic ablation: targeted expression of a toxin gene causes microphthalmia in transgenic mice. , 1987, Science.

[16]  G. Evans,et al.  Lens-specific expression of recombinant ricin induces developmental defects in the eyes of transgenic mice. , 1988, Genes & development.

[17]  H. Wilkens.  Evolution and Genetics of Epigean and Cave Astyanax fasciatus (Characidae, Pisces) , 1988 .

[18]  S. Krauss,et al.  Zebrafish pax[zf‐a]: a paired box‐containing gene expressed in the neural tube. , 1991, The EMBO journal.

[19]  M. Westerfield,et al.  Sequence and expression pattern of pax-6 are highly conserved between zebrafish and mice. , 1992, Development.

[20]  S. Ben‐Sasson,et al.  Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation , 1992, The Journal of cell biology.

[21]  M. Saha,et al.  Vertebrate eye development. , 1992, Current opinion in genetics & development.

[22]  D. Bok,et al.  The retinal pigment epithelium: a versatile partner in vision , 1993, Journal of Cell Science.

[23]  J. Dowling,et al.  Early‐eye morphogenesis in the zebrafish, Brachydanio rerio , 1994, The Journal of comparative neurology.

[24]  D. Pasko,et al.  Pax-6 is first expressed in a region of ectoderm anterior to the early neural plate: implications for stepwise determination of the lens. , 1994, Developmental biology.

[25]  W. Gehring,et al.  Homology of the eyeless gene of Drosophila to the Small eye gene in mice and Aniridia in humans. , 1994, Science.

[26]  R. DePinho,et al.  p53-dependent apoptosis produced by Rb-deficiency in the developing mouse lens , 1994, Nature.

[27]  S. Yokoyama,et al.  Initial mutational steps toward loss of opsin gene function in cavefish. , 1995, Molecular biology and evolution.

[28]  I. Jackson,et al.  The retinal pigmented epithelium is required for development and maintenance of the mouse neural retina , 1995, Current Biology.

[29]  I. Hanson,et al.  Pax6: more than meets the eye. , 1995, Trends in genetics : TIG.

[30]  D. Davidson,et al.  The role of Pax-6 in eye and nasal development. , 1995, Development.

[31]  P. Callaerts,et al.  Induction of ectopic eyes by targeted expression of the eyeless gene in Drosophila. , 1995, Science.

[32]  R. Sommer,et al.  Evolution of nematode vulval fate patterning. , 1996, Developmental biology.

[33]  A. Cvekl,et al.  Lens development and crystallin gene expression: many roles for Pax‐6 , 1996, BioEssays : news and reviews in molecular, cellular and developmental biology.

[34]  L. Niswander,et al.  Requirement for BMP Signaling in Interdigital Apoptosis and Scale Formation , 1996, Science.

[35]  H. Wilkens,et al.  Comparative analysis of Pax-6 sequence and expression in the eye development of the blind cave fish Astyanax fasciatus and its epigean conspecific. , 1997, Molecular biology and evolution.

[36]  W. Harris,et al.  Xenopus Pax-6 and retinal development. , 1997, Journal of neurobiology.