BioProject

The Otx2 homeobox transcription factor is essential for gastrulation and early neural development. More...

The Otx2 homeobox transcription factor is essential for gastrulation and early neural development. We generated Otx2 conditional knockout (cKO) mice to investigate its roles in telencephalon development after E9.0. We conducted transcriptional profiling and in situ hybridization to identify genes de-regulated in Otx2 cKO ventral forebrain. In parallel, we used ChIP-seq to identify enhancer elements, OTX2 binding motif, and which de-regulated genes are likely direct targets of Otx2 transcriptional regulation. We found that Otx2 was essential in septum specification; regulation of Fgf signaling in the rostral telencephalon; and medial ganglionic eminence (MGE) patterning, neurogenesis, and oligodendrogenesis. Within the MGE, Otx2 was required for ventral but not dorsal identity; this is the first demonstration of a transcription factor that contributes to regional patterning within the MGE. Overall design: We used an Otx2flox (Otx2f) allele with RxCre, Cre-line, to abrogate Otx2 expression ~E8.5 and ~E10.0. RxCre mice express Cre throughout the forebrain, except in the caudal dorsomedial domain that includes the choroid plexus and cortical hem. We compared mRNA expression in the ganglionic eminences and septum of RxCre conditional knock out (cKO) and control mouse embryos at E12.5. Less...