Xenopus Pax-6 and retinal development.

We have cloned a homolog of Pax-6 in Xenopus laevis. Its deduced amino acid sequence has a 95% overall identity with Pax-6 homologs in other vertebrates. It is expressed early in development in cells fated to form the eye and parts of the forebrain, hindbrain, and spinal cord. It has two phases of expression in the eye. In the early phase, from stage 12.5 to stage 33/34, Xenopus Pax-6 is expressed throughout the developing retina. In the late phase, after stage 33/34, it is excluded from mature cells in the outer half of the retina and from cells in the ciliary marginal zone, remaining only in amacrine and ganglion cells. Misexpression of Pax-6 early in development results in axial defects, but no specific eye phenotype is observed. Targeted misexpression in the retina at later stages does not result in any significant bias toward formation of amacrine or ganglion cells or away from photoreceptors. Ectopic expression of the proneural gene NeuroD alters the pattern of Pax-6, substantially reducing its expression in the eye field and later reducing or eliminating the eye itself. Our results show that Pax-6 expression appears to be necessary, but not sufficient, for eye formation in Xenopus.

[1]  J. Sambrook,et al.  Molecular Cloning: A Laboratory Manual , 2001 .

[2]  Stephen W. Wilson,et al.  Antibodies against Pax6 immunostain amacrine and ganglion cells and neuronal progenitors, but not rod precursors, in the normal and regenerating retina of the goldfish. , 1996, Journal of neurobiology.

[3]  N. Copeland,et al.  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. , 1995, Development.

[4]  W. Harris,et al.  Fate of the anterior neural ridge and the morphogenesis of the Xenopus forebrain. , 1995, Journal of neurobiology.

[5]  H. Horvitz,et al.  Patterning of the Caenorhabditis elegans head region by the Pax-6 family member vab-3 , 1995, Nature.

[6]  S. W. Emmons,et al.  Specification of sense-organ identity by a Caenorhabditis elegans Pax-6 homologue , 1995, Nature.

[7]  P. Good,et al.  Dorsal-ventral patterning and differentiation of noggin-induced neural tissue in the absence of mesoderm. , 1995, Development.

[8]  H. Weintraub,et al.  Conversion of Xenopus ectoderm into neurons by NeuroD, a basic helix-loop-helix protein. , 1995, Science.

[9]  A. Cvekl,et al.  Pax-6 is essential for lens-specific expression of zeta-crystallin. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

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

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

[12]  W. Harris,et al.  Xotch inhibits cell differentiation in the xenopus retina , 1995, Neuron.

[13]  Stephen W. Wilson,et al.  Regulatory gene expression boundaries demarcate sites of neuronal differentiation in the embryonic zebrafish forebrain , 1994, Neuron.

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

[15]  C. Zuker,et al.  On the evolution of eyes: would you like it simple or compound? , 1994, Science.

[16]  H. Weintraub,et al.  Expression of achaete-scute homolog 3 in Xenopus embryos converts ectodermal cells to a neural fate. , 1994, Genes & development.

[17]  H. Weintraub,et al.  Xenopus embryos regulate the nuclear localization of XMyoD. , 1994, Genes & development.

[18]  M. Goulding,et al.  Signals from the notochord and floor plate regulate the region-specific expression of two Pax genes in the developing spinal cord. , 1993, Development.

[19]  R. Adler.  Determination of cellular types in the retina. , 1993, Investigative ophthalmology & visual science.

[20]  S. Saule,et al.  Structure and DNA-binding properties of Pax-QNR, a paired box- and homeobox-containing gene. , 1993, Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research.

[21]  I. Hanson,et al.  Molecular genetics of the Pax gene family. , 1992, Current opinion in cell biology.

[22]  P. Gruss,et al.  Pax-5 is expressed at the midbrain-hindbrain boundary during mouse development , 1992, Mechanisms of Development.

[23]  R. Maas,et al.  Genomic structure, evolutionary conservation and aniridia mutations in the human PAX6 gene , 1992, Nature Genetics.

[24]  A. Aguzzi,et al.  Pax-5 encodes the transcription factor BSAP and is expressed in B lymphocytes, the developing CNS, and adult testis. , 1992, Genes & development.

[25]  S. Hodgson,et al.  The human PAX6 gene is mutated in two patients with aniridia , 1992, Nature Genetics.

[26]  W. Harris,et al.  Two cellular inductions involved in photoreceptor determination in the Xenopus retina , 1992, Neuron.

[27]  G. Saunders,et al.  Cloning and characterization of the murine homolog of the human aniridia gene , 1992 .

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

[29]  K. Palczewski,et al.  Anti-rhodopsin monoclonal antibodies of defined specificity: Characterization and application , 1991, Vision Research.

[30]  L. Strong,et al.  Positional cloning and characterization of a paired box- and homeobox-containing gene from the aniridia region , 1991, Cell.

[31]  G. Saunders,et al.  Mouse Small eye results from mutations in a paired-like homeobox-containing gene , 1991, Nature.

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

[33]  P. Gruss,et al.  Pax-6, a murine paired box gene, is expressed in the developing CNS. , 1991, Development.

[34]  P Gruss,et al.  Pax: a murine multigene family of paired box-containing genes. , 1991, Genomics.

[35]  M. Goulding,et al.  The molecular basis of the undulated/Pax-1 mutation , 1991, Cell.

[36]  M. Goulding,et al.  Pax‐3, a novel murine DNA binding protein expressed during early neurogenesis. , 1991, The EMBO journal.

[37]  C. Desplan,et al.  The paired box encodes a second DNA-binding domain in the paired homeo domain protein. , 1991, Genes & development.

[38]  P. Gruss,et al.  The murine paired box gene, Pax7, is expressed specifically during the development of the nervous and muscular system , 1990, Mechanisms of Development.

[39]  D. Simon,et al.  Pax8, a murine paired box gene expressed in the developing excretory system and thyroid gland. , 1990, Development.

[40]  R. Grainger,et al.  Early tissue interactions leading to embryonic lens formation in Xenopus laevis. , 1990, Developmental biology.

[41]  E. Knapik,et al.  Spatially and temporally restricted expression of Pax2 during murine neurogenesis. , 1990, Development.

[42]  P. Gruss,et al.  Pax2, a new murine paired-box-containing gene and its expression in the developing excretory system. , 1990, Development.

[43]  C. Cepko,et al.  Lineage-independent determination of cell type in the embryonic mouse retina , 1990, Neuron.

[44]  W. Harris,et al.  Mapping of the presumptive brain regions in the neural plate of Xenopus laevis. , 1990, Journal of neurobiology.

[45]  Pierre Gönczy,et al.  A single amino acid can determine the DNA binding specificity of homeodomain proteins , 1989, Cell.

[46]  R. Wetts,et al.  Cell lineage analysis reveals multipotent precursors in the ciliary margin of the frog retina. , 1989, Developmental biology.

[47]  M. Noll,et al.  Conservation of the paired domain in metazoans and its structure in three isolated human genes. , 1989, The EMBO journal.

[48]  M. Levine,et al.  Synergistic activation and repression of transcription by Drosophila homeobox proteins , 1989, Cell.

[49]  W. Herr,et al.  The ubiquitous octamer-binding protein Oct-1 contains a POU domain with a homeo box subdomain. , 1988, Genes & development.

[50]  K. Kao,et al.  The entire mesodermal mantle behaves as Spemann's organizer in dorsoanterior enhanced Xenopus laevis embryos. , 1988, Developmental biology.

[51]  R. Wetts,et al.  Multipotent precursors can give rise to all major cell types of the frog retina. , 1988, Science.

[52]  C. Holt,et al.  Cellular determination in the xenopus retina is independent of lineage and birth date , 1988, Neuron.

[53]  M. Noll,et al.  Structure of two genes at the gooseberry locus related to the paired gene and their spatial expression during Drosophila embryogenesis. , 1987, Genes & development.

[54]  J M Slack,et al.  Fate map for the 32-cell stage of Xenopus laevis. , 1987, Development.

[55]  D. Melton,et al.  Expression of Xenopus N-CAM RNA in ectoderm is an early response to neural induction. , 1987, Development.

[56]  M. Noll,et al.  Conservation of a large protein domain in the segmentation gene paired and in functionally related genes of Drosophila , 1986, Cell.

[57]  M. Noll,et al.  Structure of the segmentation gene paired and the Drosophila PRD gene set as part of a gene network , 1986, Cell.

[58]  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.

[59]  M. Kozak.  Point mutations define a sequence flanking the AUG initiator codon that modulates translation by eukaryotic ribosomes , 1986, Cell.

[60]  M. Kozak,et al.  Point mutations close to the AUG initiator codon affect the efficiency of translation of rat preproinsulin in vivo , 1984, Nature.

[61]  J. Gerhart,et al.  Axis determination in eggs of Xenopus laevis: a critical period before first cleavage, identified by the common effects of cold, pressure and ultraviolet irradiation. , 1983, Developmental biology.

[62]  R. Northcutt,et al.  Nuclear organization of the bullfrog diencephalon , 1983, The Journal of comparative neurology.

[63]  Christine Holt,et al.  Cell movements in Xenopus eye development , 1980, Nature.

[64]  F. Sanger,et al.  DNA sequencing with chain-terminating inhibitors. , 1977, Proceedings of the National Academy of Sciences of the United States of America.

[65]  J. Faber,et al.  Normal table of Xenopus laevis. , 1994 .

[66]  T. Matsuo.  The genes involved in the morphogenesis of the eye. , 1993, Japanese journal of ophthalmology.

[67]  R. Harland,et al.  In situ hybridization: an improved whole-mount method for Xenopus embryos. , 1991, Methods in cell biology.