The role of Pax6 in forebrain development

Abstract

Pax6 encodes a highly conserved transcriptional regulator with two DNA-binding motifs, a paired domain and a paired-like homeodomain. Humans carrying PAX6 loss-of-function mutations suffer from abnormal development of the eyes (congenital aniridia) and brain. Small eye mice carrying Pax6 loss-of-function mutations provide a good model for these human conditions. Their analysis has demonstrated the critical importance of this transcription factor in multiple cell types and at several key stages of forebrain development. In the forebrain, Pax6 is critical for the establishment of the pallial-subpallial boundary, which separates dorsal (future cerebral cortex) and ventral (future striatum) telencephalic regions. Levels of Pax6 expression are critically important for cortical progenitor proliferation and its presence in a rostro-lateral(high) to caudo-medial(low) gradient in the cortex is necessary to establish rostro-lateral identities. Furthermore, axon guidance is disrupted in Pax6⁻/⁻ mutants: the majority of thalamocortical axons fail to enter the ventral telencephalon and those that do are unable to innervate their cortical targets. The extent to which the effects of Pax6 later in development are secondary to its effects in early patterning and proliferation remains largely unknown. This is likely to be clarified by future studies on the molecular mechanisms of action of Pax6 and, in particular, the identification of its downstream target genes. Such studies should also help generate an increasingly coherent understanding of how this pleiotropic transcription factor becomes involved in so many facets of neural development.

MicroRNA-375 targets PAX6 and inhibits the viability, migration and invasion of human breast cancer MCF-7 cells

“…PAX6 is a member of the PAX gene family and acts as a key regulator in the development of the eyes, central nervous system and pancreas (15,32,33). Furthermore, it has been demonstrated that PAX6 serves an oncogenic role in breast cancer.…”

Irx3 and Pax6 establish differential competence for Shh-mediated induction of GABAergic and glutamatergic neurons of the thalamus

“…Pax6 is expressed throughout the forebrain from early developmental stages onward and has been implicated in multiple processes, including forebrain patterning, FMB positioning, boundary formation, and axonogenesis (14). At the time of thalamus induction, the posterior border of Pax6 expression precisely marks the FMB.…”

“…4I) (31). Previously Pax6 has been implicated in axonogenesis in the forebrain (11,14,28,32,33), prompting us to investigate whether the ectopically induced cTh neurons in the midbrain form thalamus-like projections. GFP electroporations into the tectum led to only a few posterior projections joining the lateral longitudinal fascicle, whereas ectopic cTh neurons induced by coexpression of Pax6 and SmoM2 in the midbrain formed abnormal projections growing in different directions depending on the specific location of their cell bodies in the tectum (Fig.…”

“…Activation of the Shh pathway failed to induce thalamic gene expression in the dorsal midbrain (tectum), although Irx3 is expressed there. The paired domain/homeodomain transcription factor Pax6 is expressed throughout the forebrain but not in the midbrain, and one of its early roles is the positioning of the FMB (10)(11)(12)(13)(14). Thalamocortical projections are absent and the expression of several regulatory genes is changed in the thalamus of rats and mice lacking Pax6 function, indicating that this gene is essential for thalamogenesis (15,16).…”

Horizontal Basal Cell-Specific Deletion ofPax6Impedes Recovery of the Olfactory Neuroepithelium Following Severe Injury

“…The transcription factor Pax6 is highly conserved among vertebrates and is essential for a wide variety of developmental processes within the central nervous system (CNS), sensory organs, and the endocrine system [15][16][17][18][19]. Homozygous Pax6 mutant mice (Pax6…”