Cfdp1 controls the cell cycle and neural differentiation in the zebrafish cerebellum and retina

Abstract

Background: Although the cell cycle and cell differentiation should be coordinately regulated to generate a variety of neurons in the brain, the molecules that are involved in this coordination still remain largely unknown. In this study, we analyzed the roles of a nuclear protein Cfdp1, which is thought to be involved in chromatin remodeling, in zebrafish neurogenesis. Results: Zebrafish cfdp1 mutants maintained the progenitors of granule cells (GCs) in the cerebellum, but showed defects in their differentiation to GCs. cfdp1 mutants showed an increase in phospho-histone 3 (pH 3)-positive cells and apoptotic cells, as well as a delayed cell cycle transition from the G2 to the M phase in the cerebellum. The inhibition of tp53 prevented apoptosis but not GC differentiation in the cfdp1 mutant cerebellum. A similar increase in apoptotic cells and pH 3-positive cells, and defective cell differentiation, were observed in the cfdp1 mutant retina. Although mitotic spindles formed, mitosis was blocked before anaphase in both the cerebellum and retina of cfdp1 mutant larvae. Furthermore, expression of the G2/mitotic-specific cyclin B1 gene increased in the cfdp1 mutant cerebellum.Conclusions: Our findings suggest that Cfdp1 regulates the cell cycle of neural progenitors, thereby promoting neural differentiation in the brain.

High-resolution genome topology of human retina uncovers super enhancer-promoter interactions at tissue-specific and multifactorial disease loci

“…Conservation of this genomic region from zebrafish to mammals 54 further underscores the importance of regulatory elements contained within. Notably, zebrafish mutants of Cfdp1 exhibit a loss of Neurod1 positive cells in the retina 55 . Altogether, this places regulation of CFDP1 expression in the retina as a strong candidate for AMD risk.…”

Cfdp1 Is Essential for Cardiac Development and Function

“…Studies in Drosophila melanogaster have shown that the loss of the BCNT gene Yeti causes lethality before pupation and that it mechanistically provides a chaperone-like activity that is required in higher-order chromatin organization by its interaction with histone variant H2A.V and chromatin remodeling machinery [16]. Recently, it was shown that the zebrafish gazami mutants carry a point mutation in the 3 end of the cfdp1 gene, resulting in a truncated protein [17]. It is proposed that cfdp1 controls neural differentiation and the cell cycle in the cerebellum and retina.…”

CFDP1 promotes hepatocellular carcinoma progression through activating NEDD4/PTEN/PI3K/AKT signaling pathway

“…The biological function of CFDP1 is unclear. However, studies have shown that the protein is involved in the maintenance of higher‐order chromatin tissue and influences the progression of the cell cycle 11 . Previous research reports have indicated that blocking the activity of CFDP1 with antibodies results in decreased cell viability, increased number of apoptotic cells, and reduced the extent of proliferation 12 .…”