Hibi, M. | bioRxiv Science

bioRxiv2020

Gsx2 is involved in specification of neurons in the inferior olivary nuclei from Ptf1a-expressing neuronal progenitors in zebrafish

Neurons in the inferior olivary nuclei (IO neurons) send climbing fibers to Purkinje cells to elicit functions of the cerebellum. IO neurons and Purkinje cells are derived from neural progenitors expressing the proneural gene ptf1a. In this study, we found that the homeobox gene gsx2 was co-expressed with ptf1a in IO progenitors in zebrafish. Both gsx2 and ptf1a zebrafish mutants showed a strong reduction or loss of IO neurons. The expression of ptf1a was not affected in gsx2 mutants and vice versa. In IO progenitors, the ptf1a mutation increased apoptosis whereas the gsx2 mutation did not, suggesting that ptf1a and gsx2 are independently regulated and have distinct roles. The fibroblast growth factors (Fgf) 3/8a and retinoic acid signals negatively and positively, respectively, regulated gsx2 expression and thereby the development of IO neurons. mafba and hox genes are at least partly involved in the Fgf- and retinoic acid-dependent regulation of IO neuronal development. Our results indicate that gsx2 mediates the rostro-caudal positional signals to specify the identity of IO neurons from ptf1a-expressing neural progenitors. SummaryThe homeobox gene gsx2 mediates rostro-caudal positional signaling to specify the identify of neurons in the inferior olivary nuclei from neural progenitors expressing the proneural gene ptf1a.

developmental biology↗

bioRxiv2017

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

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.

developmental biology↗