Pax6Modulates the Dorsoventral Patterning of the Mammalian Telencephalon

Abstract

The Pax6 gene encodes a transcription factor with a restricted expression in the ventricular zone of the pallium and subpallium. We tested whether the function of Pax6 is necessary for the correct patterning and morphogenesis of the vertebrate telencephalon. Homozygous embryos of the Pax6/Small eye mutant lack functional PAX6 protein because of a point mutation of the gene. In the mutant Small eye embryos we detected a ventralization of the molecular patterning of the telencephalon at two borders, the pallium/subpallium and the lateral/medial ganglionic eminence. The results indicate that Pax6 controls the lateral limit of the expression of Nkx2.1, Shh, and Lhx6 in the prechordal neural tube, the telencephalon. This finding is in agreement with previous studies and supports a model for a common genetic mechanism for modulation of the dorsoventral patterning of the prechordal and epichordal CNS. The pattern defects caused by the loss of Pax6 function result in multiple morphological abnormalities in the Small eye brain: dysgenesis of the piriform, insular, and lateral cortices, the claustrum-endopiriform nucleus, and a failure in the differentiation of a subpopulation of the cortical precursors. Together the results demonstrate that Pax6 has an essential role for the modulation of the dorsoventral patterning of the embryonic telencephalon, influencing thereby the forebrain morphogenesis.

Identification and characterization of a novel transcript down‐regulated in Dlx1/Dlx2 and up‐regulated in Pax6 mutant telencephalon

“…These findings have shown that genes normally expressed ventrally, such as Dlx1, extend their expression into the pallium (Stoykova et al, 2000;Toresson et al, 2000;Yun et al, 2001). Of interest, while Dlx1 and Mash1 expression expands into the VZ of the Pax6 -/-pallium, mEvf-1 expression spreads in a complementary manner into the SVZ and cortical plate.…”

“…Of interest, while Dlx1 and Mash1 expression expands into the VZ of the Pax6 -/-pallium, mEvf-1 expression spreads in a complementary manner into the SVZ and cortical plate. Ectopic expression of subpallial genes in Pax6 -/-pallium may be explained by re-specification of dorsal cells to a more ventral fate (Stoykova et al, 1996(Stoykova et al, , 2000Toresson et al, 2000;Yun et al, 2001) and/or by an increased tangential migration from the ventral to dorsal telencephalon (Chapouton et al, 1999).…”

“…The ventral pallium and dorsal subpallium are separated by a boundary region that expresses a distinct set of developmental control genes (for example Dlx1 and Dlx2 on the subpallial side and Pax6 on the pallial side) and, later, by a morphologically identifiable radial glial palisade (Gotz et al, 1998;Chapouton et al, 1999). The Pax6 and Dlx homeobox genes have central roles in controlling the development of the pallium and subpallium, respectively (Stoykova et al, 1996(Stoykova et al, , 2000Anderson et al, 1997a,b).…”

“…In the embryonic telencephalon, the expression of Pax6 is largely confined to the mitotically active ventricular neuroepithelium of the pallium, although low expression is also present in the lateral ganglionic eminence (Stoykova et al, 1996(Stoykova et al, , 2000Toresson et al, 2000;Yun et al, 2001;Stenman et al, 2003). Cortical development is severely compromised in the Pax6 -/-mutant (Stoykova et al, 1996(Stoykova et al, , 2000Caric et al, 1997;Warren et al, 1999;Toresson et al, 2000;Yun et al, 2001).…”

“…Cortical development is severely compromised in the Pax6 -/-mutant (Stoykova et al, 1996(Stoykova et al, , 2000Caric et al, 1997;Warren et al, 1999;Toresson et al, 2000;Yun et al, 2001). There is a severe defect of dorsoventral patterning of the telencephalon that particularly affects the pallium, where there is ectopic expression of subpallial regulatory genes, including Dlx1, Gsh2, Mash1, Six3, and Vax1 (Stoykova et al, 2000;Toresson et al, 2000;Yun et al, 2001). In addition, Pax6 mutants exhibit subpallial defects, as expression of Nkx2.1 and Lhx6, usually restricted to the medial ganglionic eminence (MGE), expands into the adjacent lateral ganglionic eminence (LGE; Stoykova et al, 2000).…”