Abstract
BackgroundNotch signaling is mainly regulated by Notch1 during development of chicken germ stem cells; however, the molecular mechanisms that contribute to generation of these germ stem cells have not been thoroughly investigated.ResultsIn our studies, Overexpression of the Notch1 NICD promoted development of the reproductive ridge, but inhibited the formation of seminiferous tubules. The formation efficiency of PGCs in the reproductive ridge following overexpression of NICD (7.5% ± 0.11) was significantly higher than that (4.9% ± 0.17, p < 0.05) following inhibition of NICD, While the formation efficiency of spermatogonial stem cells (SSCs) in the testes (12.7% ± 0.08) was significantly lower after NICD overexpression than that after inhibition of NICD (16.3% ± 0.16, p < 0.05). Using co-immunoprecipitation, we found that this anomaly stemmed from the reversal of dissociation of the Notch-regulated transcription factor CBF-1/RBP co-suppression complex during the differentiation of PGCs into SSCs. This dissociation of the CBF-1/RBP co-suppressing complex during the differentiation of ESCs into PGCs resulted in the release of HDAC1 and HDAC2 and the recruitment of mastermind-like 1 to form a coactive complex to promote the expression of the downstream transcription suppressor hairy/enhancer of split-1. Dynamic expression of transducin-like enhancer of split 3, TLE4, and C-terminal binding protein 2 during further differentiation of PGCs inhibited the dissociation of the CBF-1/RBP co-suppression complex and inhibited the expression of the downstream genes.ConclusionsIn summary, Notch signaling plays diametrically opposing roles during normal development of chicken PGCs and SSCs, and these functions was determined by the expression of NICD, changes in the CBF-1/RBP complex composition, and histone modification.
Highlights
Notch signaling is mainly regulated by Notch1 during development of chicken germ stem cells; the molecular mechanisms that contribute to generation of these germ stem cells have not been thoroughly investigated
Notch1 regulates gonadal development in chicken germ cells The Notch signaling pathway is highly conserved throughout evolution and is involved in the cell differentiation process [14] through the functions of Notch1, Notch2, Notch3, and Notch4 [15]
These observations suggest that the Notch signaling pathway may only be regulated by Notch1 during germ cell formation in chicken
Summary
Notch signaling is mainly regulated by Notch during development of chicken germ stem cells; the molecular mechanisms that contribute to generation of these germ stem cells have not been thoroughly investigated. Research on in vitro differentiation of germ cells from embryonic stem cells (ESCs) has advanced considerably, several gaps remain. Low repeatability and efficiency in induction of germ cell differentiation and a lack of clarity about the molecular regulation of Several studies have investigated aspects of the Notch signaling pathway. Zuo et al Cell Biosci (2018) 8:40 cells (SSCs) with brain-derived neurotrophic factor and detected increased expression of NUMB, a protein that causes the degradation of the intracellular domain of Notch (NICD), as well as the inhibition of Notch target genes. By screening mutations in Notch, Huang et al found that a decrease in Notch expression upregulated hairy/enhancer of split (HES-5) and downregulated Neurog, a SSCs differentiation marker [8]
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