PUBLICATION

Hcfc1a regulates neural precursor proliferation and asxl1 expression in the developing brain

Authors
Castro, V.L., Reyes, J.F., Reyes-Nava, N.G., Paz, D., Quintana, A.M.
ID
ZDB-PUB-200612-1
Date
2020
Source
BMC Neuroscience   21: 27 (Journal)
Registered Authors
Quintana, Anita
Keywords
Brain development, HCFC1, Neural precursor cells (NPCs), asxl1
Datasets
GEO:GSE132864
MeSH Terms
  • Animals
  • Brain/growth & development*
  • Brain/metabolism
  • Cell Differentiation/genetics*
  • Cell Proliferation/genetics*
  • Cells, Cultured
  • Gene Expression Regulation/genetics*
  • Host Cell Factor C1/genetics*
  • Neural Stem Cells/physiology
  • Neurogenesis
  • Neurons/metabolism
  • Transcription Factors/metabolism
  • Zebrafish/genetics
  • Zebrafish Proteins/genetics*
PubMed
32522152 Full text @ BMC Neurosci.
Abstract
Precise regulation of neural precursor cell (NPC) proliferation and differentiation is essential to ensure proper brain development and function. The HCFC1 gene encodes a transcriptional co-factor that regulates cell proliferation, and previous studies suggest that HCFC1 regulates NPC number and differentiation. However, the molecular mechanism underlying these cellular deficits has not been completely characterized.
Here we created a zebrafish harboring mutations in the hcfc1a gene (the hcfc1aco60/+ allele), one ortholog of HCFC1, and utilized immunohistochemistry and RNA-sequencing technology to understand the function of hcfc1a during neural development.
The hcfc1aco60/+ allele results in an increased number of NPCs and increased expression of neuronal and glial markers. These neural developmental deficits are associated with larval hypomotility and the abnormal expression of asxl1, a polycomb transcription factor, which we identified as a downstream effector of hcfc1a. Inhibition of asxl1 activity and/or expression in larvae harboring the hcfc1aco60/+ allele completely restored the number of NPCs to normal levels.
Collectively, our data demonstrate that hcfc1a regulates NPC number, NPC proliferation, motor behavior, and brain development.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping