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

Abstract

The basic Helix-Loop-Helix transcription factor Atoh1 is required for the specification of multiple neuron types in the mammalian hindbrain including tegmental, precerebellar output neurons and cerebellar granule neurons. How a single proneural gene specifies so many neuron types from a single progenitor zone, the upper rhombic lip (URL), is not known. Here we use the zebrafish to explore the role of atoh1 in cerebellar neurogenesis. Using transgenic reporters we show that zebrafish atoh1c-expressing cells give rise to tegmental and granule cell populations that, together with previously described atoh1a-derived neuron populations, resemble the diversity of atoh1 derivatives observed in mammals. Using genetic mutants we find that of the three zebrafish atoh1 paralogs, atoh1c and atoh1a are required for the full complement of granule neurons in the zebrafish cerebellum. Interestingly, atoh1a and atoh1c specify non-overlapping granule populations, indicating that fish use multiple atoh1 genes to generate granule neuron diversity that is not detected in mammals. By live imaging of neurogenesis at the URL we show that atoh1c is not required for the specification of granule neuron progenitors but promotes their delamination from the URL epithelium and this process is critical for neuronal maturation. This study thus provides a better understanding of how proneural transcription factors regulate neurogenesis in the vertebrate cerebellum.\n\nSummary statementatoh1 genes specify distinct populations of tegmental and granule neurons in the zebrafish hindbrain and promote their delamination from the neuroepithelium, a process critical for neuronal maturation.