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
-
- Neurons/metabolism
- Zebrafish Proteins/genetics*
- Cells, Cultured
- Host Cell Factor C1/genetics*
- Brain/growth & development*
- Brain/metabolism
- Zebrafish/genetics
- Cell Proliferation/genetics*
- Transcription Factors/metabolism
- Neurogenesis
- Animals
- Cell Differentiation/genetics*
- Gene Expression Regulation/genetics*
- Neural Stem Cells/physiology
- PubMed
- 32522152 Full text @ BMC Neurosci.
Citation
Castro, V.L., Reyes, J.F., Reyes-Nava, N.G., Paz, D., Quintana, A.M. (2020) Hcfc1a regulates neural precursor proliferation and asxl1 expression in the developing brain. BMC Neuroscience. 21:27.
Abstract
Background 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.
Methods 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.
Results 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.
Conclusion Collectively, our data demonstrate that hcfc1a regulates NPC number, NPC proliferation, motor behavior, and brain development.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping