Cerebellar Neuron Diversity in the Zebrafish: More atoh1 Genes for More atoh1 Fates?

Abstract

During mammalian cerebellar development, a single Atoh1 basic‐helix‐loop‐helix transcription factor is required sequentially for the specification of multiple neuron types. The zebrafish genome encodes three paralagous atoh1 genes, atoh1a, atoh1b and atoh1c with overlapping but distinct spatio‐temporal expression patterns in the developing cerebellum. (The presence of extra paralogs in fish genomes is due to a whole‐genome duplication at the base of the teleost lineage). We have studied the roles of zebrafish atoh1 paralogs using transgenic reporters to mark atoh1c‐and atoh1a‐specified neurons, as well using CRISPR/Cas9‐generated mutant alleles in all three genes. Our analysis suggests that additional atoh1 genes are the source of additional neuronal diversity in the zebrafish cerebellum. atoh1c‐expressing cells are organized in two distinct domains: an early expression domain at the mid‐hindbrain boundary gives rise to an extracerebellar population in rhombomere 1 and an upper rhombic lip domain gives rise to granule cells that populate the four granule neuron territories of the fish cerebellum. Atoh1a‐expressing cells at the URL give rise to a separate population of granule neurons that do not overlap with the atoh1c populations. Consistent with this, atoh1a and atoh1c are both required for the specification of the full complement of granule neurons. These results suggest that zebrafish atoh1 duplicates generate granule neuron diversity that is not detected in mammals.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.