Dynamic Expression and New Functions of Early B Cell Factor 2 in Cerebellar Development

AbstractThe collier/Olf1/EBF family genes encode helix-loop-helix transcription factors (TFs) highly conserved in evolution, initially characterized for their roles in the immune system and in various aspects of neural development. TheEarly B cell Factor 2 (Ebf2) gene plays an important role in the establishment of cerebellar cortical topography and in Purkinje cell (PC) subtype specification. In the adult cerebellum,Ebf2 is expressed in zebrin II (ZII)-negative PCs, where it suppresses the ZII+ molecular phenotype. However, it is not clear whetherEbf2 is restricted to a PC subset from the onset of its expression or is initially distributed in all PCs and silenced only later in the prospective ZII+ subtype. Moreover, the dynamic distribution and role ofEbf2 in the differentiation of other cerebellar cells remain unclarified. In this paper, by genetic fate mapping, we determine thatEbf2 mRNA is initially found in all PC progenitors, suggesting that unidentified upstream factors silence its expression before completion of embryogenesis. Moreover we showEbf2 activation in an early born subset of granule cell (GC) precursors homing in the anterior lobe. Conversely,Ebf2 transcription is repressed in other cerebellar cortex interneurons. Last, we show that, althoughEbf2 only labels the medial cerebellar nuclei (CN) in the adult cerebellum, the gene is expressed prenatally in projection neurons of all CN. Importantly, inEbf2 nulls, fastigial nuclei are severely hypocellular, mirrori...
Source: The Cerebellum - Category: Neurology Source Type: research