Dlx-Dependent and -Independent Regulation of Olfactory Bulb Interneuron Differentiation

Olfactory bulb interneuron development is a complex multistep process that involves cell specification in the ventral telencephalon, tangential migration into the olfactory bulb, and local neuronal maturation. Although several transcription factors have been implicated in this process, how or when they act remains to be elucidated. Here we explore the mechanisms that result in olfactory bulb interneuron defects inDlx1&2−/−(distal-less homeobox 1 and 2) andMash1−/−(mammalian achaete-schute homolog 1) mutants. We provide evidence thatDlx1&2andMash1regulate parallel molecular pathways that are required for the generation of these cells, thereby providing new insights into the mechanisms underlying olfactory bulb development. The analysis also defined distinct anatomical zones related to olfactory bulb development. Finally we show thatDlx1&2are required for promoting tangential migration to the olfactory bulb, potentially via regulating the expression ofErbB4(v-erb-a erythroblastic leukemia viral oncogene homolog 4),Robo2(roundabout homolog 2),Slit1(slit homolog 1), andPK2(prokineticin 2), which have all been shown to play essential roles in this migration.