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

Aurora Badaloni, Filippo Casoni, Laura Croci, Francesca Chiara, Antonella Bizzoca, Gianfranco Gennarini, Ottavio Cremona, Richard Hawkes, G. Giacomo Consalez

Research output: Contribution to journalArticle

Abstract

The 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. The Early 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 whether Ebf2 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 of Ebf2 in the differentiation of other cerebellar cells remain unclarified. In this paper, by genetic fate mapping, we determine that Ebf2 mRNA is initially found in all PC progenitors, suggesting that unidentified upstream factors silence its expression before completion of embryogenesis. Moreover we show Ebf2 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, although Ebf2 only labels the medial cerebellar nuclei (CN) in the adult cerebellum, the gene is expressed prenatally in projection neurons of all CN. Importantly, in Ebf2 nulls, fastigial nuclei are severely hypocellular, mirroring the defective development of anterior lobe PCs. Our findings further clarify the roles of this terminal selector gene in cerebellar development.

Original languageEnglish
Pages (from-to)999-1010
Number of pages12
JournalCerebellum
Volume18
Issue number6
DOIs
Publication statusPublished - Dec 1 2019

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Keywords

  • Cerebellar cortex topography
  • Cerebellar development
  • Cerebellar granule cell subtypes
  • Cerebellar nuclei development
  • COE transcription factors
  • Ebf2 gene
  • Fastigial nuclei development
  • Purkinje cell development
  • Purkinje cell subtype specification

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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