PUBLICATION

Foxp- and Skor-family proteins control differentiation of Purkinje cells from Ptf1a and Neurogenin1-expressing progenitors in zebrafish

Authors
Itoh, T., Uehara, M., Yura, S., Wang, J.C., Fujii, Y., Nakanishi, A., Shimizu, T., Hibi, M.
ID
ZDB-PUB-240309-2
Date
2024
Source
Development (Cambridge, England)   151(7): (Journal)
Registered Authors
Hibi, Masahiko, Shimizu, Takashi
Keywords
Foxp, Neurogenin1, Ptf1a, Purkinje cells, Skor, Zebrafish
MeSH Terms
  • Animals
  • Cell Differentiation/genetics
  • Cerebellum
  • Mammals
  • Neurons/metabolism
  • Purkinje Cells*/metabolism
  • Zebrafish*/genetics
PubMed
38456494 Full text @ Development
Abstract
Cerebellar neurons, such as GABAergic Purkinje cells (PCs), interneurons (INs), and glutamatergic granule cells (GCs) are differentiated from neural progenitors expressing proneural genes including ptf1a, neurogenin1, and atoh1a/b/c. Studies in mammals previously suggested that these genes determine cerebellar neuron cell fate. However, our studies on ptf1a;neurogenin1 zebrafish mutants and lineage tracing of ptf1a-expressing progenitors have revealed that the ptf1a/neurogenin1-expressing progenitors can generate diverse cerebellar neurons including PCs, INs, and a part of GCs in zebrafish. The precise mechanisms of how each cerebellar neuron type is specified remains elusive. We found that genes encoding transcriptional regulators Foxp1b, Foxp4, Skor1b, and Skor2, which are reportedly expressed in PCs, were absent in ptf1a;neurogenin1 mutants. foxp1b;foxp4 mutants showed a strong reduction in PCs, while skor1b;skor2 mutants completely lacked PCs but instead displayed an increase in immature GCs. Misexpression of skor2 in GC progenitors expressing atoh1c suppressed GC fate. These data indicate that Foxp1b/4 and Skor1b/2 function as key transcriptional regulators in the initial step of PC differentiation from ptf1a/neurogenin1-expressing neural progenitors, while Skor1b and Skor2 control PC differentiation by suppressing their differentiation into GCs.
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