THE HEM OF THE EMBRYONIC CEREBRAL-CORTEX IS DEFINED BY THE EXPRESSIONOF MULTIPLE WNT GENES AND IS COMPROMISED IN GLI3-DEFICIENT MICE

In the developing vertebrate CNS, members of the Wnt gene family are c haracteristically expressed at signaling centers that pattern adjacent parts of the neural tube. To identify candidate signaling centers in the telencephalon, we isolated Wnt gene fragments from cDNA derived fr om embryonic mouse telencephalon. In situ hybridization experiments de monstrate that one of the isolated Wnt genes, Wnt7a, is broadly expres sed in the embryonic telencephalon, By contrast, three others, Wnt3a, 5a and a novel mouse Wnt gene, Wnt2b, are expressed only at the medial edge of the telencephalon, defining the hem of the cerebral cortex. T he Wnt-rich cortical hem is a transient, neuron-containing, neuroepith elial structure that forms a boundary between the hippocampus and the telencephalic choroid plexus epithelium (CPe) throughout their embryon ic development, Indicating a close developmental relationship between the cortical hem and the CPe, Wnt gene expression is upregulated in th e cortical hem both before and just as the CPe begins to form, and per sists until birth. In addition, although the cortical hem does not sho w features of differentiated CPe, such as expression of transthyretin mRNA, the CPe and cortical hem are linked by shared expression of memb ers of the Bmp and Msx gene families. In the extra-toes(J) (Xt(J)) mou se mutant, telencephalic CPe fails to develop, We show that Wnt gene e xpression is deficient at the cortical hem in Xt(J)/Xt(J) mice, but th at the expression of other telencephalic developmental control genes, including Wnt7a, is maintained. The XtJ mutant carries a deletion in G li3, a vertebrate homolog of the Drosophila gene cubitus interruptus ( ci), which encodes a transcriptional regulator of the Drosophila Wnt g ene, wingless, Our observations indicate that Gli3 participates in Wnt gene regulation in the vertebrate telencephalon, and suggest that the loss of telencephalic choroid plexus in XtJ mice is due to defects in the cortical hem that include Wnt gene misregulation.