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

Background Precise regulation of neural precursor cell (NPC) proliferation and differentiation is essential to ensure proper brain development and function. TheHCFC1gene 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 thehcfc1agene (thehcfc1a(co60/+)allele), one ortholog ofHCFC1, and utilized immunohistochemistry and RNA-sequencing technology to understand the function ofhcfc1aduring neural development. Results Thehcfc1a(co60/+)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 ofasxl1, a polycomb transcription factor, which we identified as a downstream effector ofhcfc1a. Inhibition ofasxl1activity and/or expression in larvae harboring thehcfc1a(co60/+)allele completely restored the number of NPCs to normal levels. Conclusion Collectively, our data demonstrate thathcfc1aregulates NPC number, NPC proliferation, motor behavior, and brain development.