Many cerebral cortical neurons and glia are produced by apical progenitors dividing at the ventricular surface of the embryonic dorsal telencephalon. Other neurons are produced by basal progenitor cells, which are derived from apical progenitors, dividing away from the ventricular surface. The transcription factor Pax6 is expressed in apical progenitors and is downregulated in basal progenitors, which upregulate the transcription factor Tbr2. Here we show that Pax6−/− cells are under-represented in the cortex of Pax6+/+↔Pax6−/− chimeras early in corticogenesis, indicating that Pax6 is required for the production of normal numbers of cortical cells. We provide evidence that this underproduction is attributable to an early depletion of the progenitor pool caused by greater than normal proportions of newly divided cells exiting the cell cycle. We show that most progenitor cells dividing away from the ventricular surface in Pax6−/− embryos fail to express the transcription factor Tbr2 and that Pax6 is required cell autonomously for Tbr2 expression in the developing cortex of Pax6+/+↔Pax6−/− chimeras. Transcription factors normally expressed ventrally in the telencephalic ganglionic eminences (Mash1, Dlx2 and Gsh2) are upregulated cell autonomously in mutant cells in the developing cortex of Pax6+/+↔Pax6−/− chimeras; Nkx2.1, which is expressed only in the medial ganglionic eminence, is not. These data indicate that early functions of Pax6 in developing cortical cells are to repress expression of transcription factors normally found in the lateral ganglionic eminence, to prevent precocious differentiation and depletion of the progenitor pool, and to induce normal development of cortical basal progenitor cells.

Patterns of growth and cell movement in the developing and adult corneal epithelium were investigated by analysing clonal patches of LacZ-expressing cells in chimeric and X-inactivation mosaic mice. It was found that cell proliferation throughout the basal corneal epithelium during embryogenesis and early postnatal life creates a disordered mosaic pattern of

Mouse embryos, homozygous for the small eye (Sey) mutation die soon after birth with severe facial abnormalities that result from the failure of the eyes and nasal cavities to develop. Mutations in the Pax6 gene are responsible for the Sey phenotype. As a general disruption of eye and nasal development occurs in the homozygous Sey embryos, it is unclear, from the mutant phenotype alone, which tissues require functional Pax6. To examine the roles for Pax6 in eye and nasal development we produced chimeric mouse embryos composed of wild-type and Sey mutant cells. In these embryos we found that mutant cells were excluded from both the lens and nasal epithelium. Both of these tissues were smaller, and in some cases absent, in chimeras with high proportions of mutant cells. The morphology of the optic cup was also severely affected in these chimeras; mutant cells were excluded from the retinal pigmented epithelium and did not intermix with wild-type cells in other regions. The evidence shows that Pax6 has distinct roles in the nasal epithelium and the principal tissue components of the embryonic eye, acting directly and cell autonomously in the optic cup and lens. We suggest that Pax6 may promote cell surface changes in the optic cup and control the fate of the ectoderm from which the lens and nasal epithelia are derived.

Background: The mouse corneal epithelium is a continuously renewing 5-6 cell thick protective layer covering the corneal surface, which regenerates rapidly when injured. It is maintained by peripherally located limbal stem cells (LSCs) that produce transient amplifying cells (TACs) which proliferate, migrate centripetally, differentiate and are eventually shed from the epithelial surface. LSC activity is required both for normal tissue maintenance and wound healing. Mosaic analysis can provide insights into LSC function, cell movement and cell mixing during tissue maintenance and repair. The present study investigates cell streaming during corneal maintenance and repair and changes in LSC function with age.

The correct Pax6 dosage is necessary for normal clonal growth during corneal development, normal limbal stem cell activity, and correct corneal epithelial cell migration. Disruption of normal cell movement in heterozygotes may be the consequence of failure of nonautonomous guidance cues. Degeneration of the corneal surface in aniridia-related keratopathy relates to both a deficiency within the limbal stem cell niche and nonautonomous diversion of corneal epithelial cell migration.