Pax6-dependent regulation of adhesive patterning, R-cadherin expression and boundary formation in developing forebrain.

Mutations in the gene for the transcription factor, Pax6, induce marked developmental abnormalities in the CNS and the eye, but the cellular mechanisms that underlie the phenotype are unknown. We have examined the adhesive properties of cells from the developing forebrain in Small eye, the Pax6 mutant mouse. We have found that the segregation normally observed in aggregates of cortical and striatal cells in an in vitro assay is lost in Small eye. This correlates with an alteration of in vivo expression of the homophilic adhesion molecule, R-cadherin. Moreover, the boundary between cortical and striatal regions of the telencephalon is dramatically altered in Small eye: radial glial fascicles do not form at the border, and the normal expression of R-cadherin and tenascin-C at the border is lost. These data suggest a link between the transcription factor, Pax6, R-cadherin expression, cellular adhesion and boundary formation between developing forebrain regions.

[1]  S. Easter,et al.  Pax-6 functions in boundary formation and axon guidance in the embryonic mouse forebrain. , 1997, Development.

[2]  M. Götz,et al.  Tenascin‐C Synthesis and Influence on Axonal Growth During Rat Cortical Development , 1997, The European journal of neuroscience.

[3]  R. Krumlauf,et al.  Altered segmental identity and abnormal migration of motor neurons in mice lacking Hoxb-1 , 1996, Nature.

[4]  C. Redies,et al.  Cadherins in the developing central nervous system: an adhesive code for segmental and functional subdivisions. , 1996, Developmental biology.

[5]  P Gruss,et al.  Dentate gyrus formation requires Emx2. , 1996, Development.

[6]  Andrew Lumsden,et al.  Patterning the Vertebrate Neuraxis , 1996, Science.

[7]  P Gruss,et al.  Forebrain patterning defects in Small eye mutant mice. , 1996, Development.

[8]  P. Brûlet,et al.  Epilepsy and brain abnormalities in mice lacking the Otx1 gene , 1996, Nature Genetics.

[9]  F. Valverde,et al.  Dynamics of Cell Migration from the Lateral Ganglionic Eminence in the Rat , 1996, The Journal of Neuroscience.

[10]  M. Götz,et al.  Selective Adhesion of Cells from Different Telencephalic Regions , 1996, Neuron.

[11]  P. Chambon,et al.  AP-2.2, a novel gene related to AP-2, is expressed in the forebrain, limbs and face during mouse embryogenesis , 1996, Mechanisms of Development.

[12]  M. Takeichi,et al.  Fetal brain subdivisions defined by R- and E-cadherin expressions: evidence for the role of cadherin activity in region-specific, cell-cell adhesion. , 1995, Developmental biology.

[13]  J. Rubenstein,et al.  T-Brain-1: A homolog of Brachyury whose expression defines molecularly distinct domains within the cerebral cortex , 1995, Neuron.

[14]  C. Redies,et al.  R-cadherin expression during nucleus formation in chicken forebrain neuromeres , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[15]  M. Seike,et al.  The reeler gene-associated antigen on cajal-retzius neurons is a crucial molecule for laminar organization of cortical neurons , 1995, Neuron.

[16]  A. LaMantia,et al.  Distinct adhesive behaviors of neurons and neural precursor cells during regional differentiation in the mammalian forebrain. , 1995, Developmental biology.

[17]  T. Curran,et al.  A protein related to extracellular matrix proteins deleted in the mouse mutant reeler , 1995, Nature.

[18]  A. Baird.  Fibroblast growth factors: activities and significance of non-neurotrophin neurotrophic growth factors , 1994, Current Opinion in Neurobiology.

[19]  Joseph Altman,et al.  Atlas of prenatal rat brain development , 1994 .

[20]  A. McMahon,et al.  Wnt-1-dependent regulation of local E-cadherin and alpha N-catenin expression in the embryonic mouse brain. , 1994, Development.

[21]  R. Krumlauf.  Hox genes in vertebrate development , 1994, Cell.

[22]  F. Valverde,et al.  Development and early postnatal maturation of the primary olfactory cortex. , 1994, Brain research. Developmental brain research.

[23]  P. Gruss,et al.  Roles of Pax-genes in developing and adult brain as suggested by expression patterns , 1994, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[24]  P. Gruss,et al.  Pax genes in development , 1994, Journal of Cell Science.

[25]  P. Gruss,et al.  Prox 1, a prospero-related homeobox gene expressed during mouse development , 1993, Mechanisms of Development.

[26]  Luis Puelles,et al.  Expression patterns of homeobox and other putative regulatory genes in the embryonic mouse forebrain suggest a neuromeric organization , 1993, Trends in Neurosciences.

[27]  A. Joyner,et al.  Dynamic expression of the murine Achaete-Scute homologue Mash-1 in the developing nervous system , 1993, Mechanisms of Development.

[28]  J. Rubenstein,et al.  Spatially restricted expression of Dlx-1, Dlx-2 (Tes-1), Gbx-2, and Wnt- 3 in the embryonic day 12.5 mouse forebrain defines potential transverse and longitudinal segmental boundaries , 1993, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[29]  A. Simeone,et al.  A vertebrate gene related to orthodenticle contains a homeodomain of the bicoid class and demarcates anterior neuroectoderm in the gastrulating mouse embryo. , 1993, The EMBO journal.

[30]  C. Redies,et al.  Expression of N‐cadherin mRNA during development of the mouse brain , 1993, Developmental dynamics : an official publication of the American Association of Anatomists.

[31]  T. Matsuo,et al.  A mutation in the Pax-6 gene in rat small eye is associated with impaired migration of midbrain crest cells , 1993, Nature Genetics.

[32]  M. Takeichi,et al.  Local and transient expression of E-cadherin involved in mouse embryonic brain morphogenesis. , 1992, Development.

[33]  J. Bolz,et al.  Formation and preservation of cortical layers in slice cultures. , 1992, Journal of neurobiology.

[34]  M. Gulisano,et al.  Two vertebrate homeobox genes related to the Drosophila empty spiracles gene are expressed in the embryonic cerebral cortex. , 1992, The EMBO journal.

[35]  Roel Nusse,et al.  Wnt genes , 1992, Cell.

[36]  J. Altman,et al.  Development of the endopiriform nucleus and the claustrum in the rat brain , 1991, Neuroscience.

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

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

[39]  D. Duboule,et al.  A mouse gene related to Distal-less shows a restricted expression in the developing forebrain , 1991, Nature.

[40]  M. Rosenfeld.  POU-domain transcription factors: pou-er-ful developmental regulators. , 1991, Genes & development.

[41]  M. Edwards,et al.  Organization of radial glia and related cells in the developing murine CNS. An analysis based upon a new monoclonal antibody marker , 1990, Neuroscience.

[42]  M. Beato.  Gene regulation by steroid hormones , 1989, Cell.

[43]  V S Caviness,et al.  Identification of radial glial cells within the developing murine central nervous system: studies based upon a new immunohistochemical marker. , 1988, Brain research. Developmental brain research.

[44]  Michael W. Miller,et al.  Use of bromodeoxyuridine-immunohistochemistry to examine the proliferation, migration and time of origin of cells in the central nervous system , 1988, Brain Research.

[45]  S. Bayer,et al.  Neurogenesis in the rat primary olfactory cortex , 1986, International Journal of Developmental Neuroscience.

[46]  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.

[47]  P. Rakić.  Guidance of neurons migrating to the fetal monkey neocortex. , 1971, Brain research.

[48]  R. C. Roberts.  Small eyes —a new dominant eye mutant in the mouse , 1967 .

[49]  S. Aizawa,et al.  Emx1 and Emx2 functions in development of dorsal telencephalon. , 1997, Development.

[50]  N. O’Rourke.  Neuronal Chain Gangs: Minireview Homotypic Contacts Support Migration into the Olfactory Bulb , 1996 .

[51]  J. Rubenstein,et al.  Homeobox gene expression during development of the vertebrate brain. , 1994, Current topics in developmental biology.

[52]  P. Gruss,et al.  Pax: genes for mice and men. , 1994, Pharmacology & therapeutics.

[53]  Richard L. Maas,et al.  Erratum: PAX6 gene dosage effect in a family with congenital cataracts, aniridia, anophthalmia and central nervous system defects (Nature Genetics 7 (463-471)) , 1994 .

[54]  G. Fishell,et al.  Dispersion of neural progenitors within the germinal zones of the forebrain , 1993, Nature.

[55]  A. McMahon.  A Super Family of Putative Developmental Signaling Molecules Related to the Proto-Oncogene Wnt-1/int-1 , 1992 .

[56]  George Paxinos,et al.  Atlas Of The Developing Rat Brain , 1991 .

[57]  G. Chalepakis,et al.  Gene regulation by steroid hormones. , 1989, Cell.

[58]  G H Sato,et al.  Growth of a rat neuroblastoma cell line in serum-free supplemented medium. , 1979, Proceedings of the National Academy of Sciences of the United States of America.

[59]  R. Sturrock,et al.  Ontogeny of the Neostriatum , 1979 .