Multiple zebrafish atoh1 genes specify a diversity of neuronal types in the zebrafish hindbrain

Abstract

The basic Helix-Loop-Helix transcription factor, Atoh1, is known to specify several neuronal subtypes including one of most abundant cell types in the vertebrate brain, cerebellar granule neurons. The function of atoh1 in the development of cerebellar granule neurons is poorly understood. Here we use the zebrafish CNS to explore the role of atoh1 in granule neuron specification and in the generation of neuronal diversity. With the use of single and compound atoh1 mutants, we show that out of the three atoh1 genes in the zebrafish genome, atoh1c plays the most prominent role in granule neuron development but together atoh1c and atoh1a are required for the full complement of granule neurons. Interestingly, atoh1a and atoh1c specify non-overlapping granule populations, indicating that fish use multiple atoh1 genes to generate additional neuronal diversity that is not detected in mammals. In addition, we have identified a novel population of atoh1c-derived neurons closely associated with the conserved noradrenergic neurons of the Locus Coeruleus. Finally, with the use of live imaging possible in zebrafish, we discovered expression of atoh1c at the rhombic lip promotes the apical detachment of granule neuron progenitors from surrounding neuroepithelium and this process is critical for neuronal maturation. This study provides us with a better understanding of how a proneural transcription factor influences neurogenesis in the vertebrate brain.