Bidirectional interaction between protocadherin 8 and the transcription factor Dbx1 regulates cerebral cortex development

Brain development requires correct tissue patterning and production of appropriate cell types. Transcription factors play essential roles in these processes, regulating the expression of target genes responsible for the specific features of neuronal subtypes. Cell adhesion molecules are key components of developmental processes that control cell sorting, migration, neurite outgrowth/guidance and synaptogenesis. To date, the link between transcription factors and cell adhesion molecules has been considered unidirectional. Here, we demonstrate that ectopic expression of Dbx1 leads to spatiotemporally restricted increased expression of Pcdh8 and cell aggregation, together with changes in neuronal identity. Surprisingly, ectopic Pcdh8 expression also induces Dbx1 expression, as well as a complete reorganisation of apico-basal polarity and dorso-ventral patterning via Notch signalling. Altogether, our work therefore points to cell adhesion molecules as unexpected, yet important, players in the regulation of cell identity and, in particular, Pcdh8 through its bidirectional interaction with the Dbx1 transcription factor.