Green tea epigallocatechin-3-gallate (EGCG) promotes neural progenitor cell proliferation and sonic hedgehog pathway activation during adult hippocampal neurogenesis

Histone cell cycle regulator (HIRA) is a histone chaperone and has been identified as an epigenetic regulator. Subsequent studies have provided evidence that HIRA plays key roles in embryonic development, but its function during early neurogenesis remains unknown. Here, we demonstrate that HIRA is enriched in neural progenitor cells, and HIRA knockdown reduces neural progenitor cell proliferation, increases terminal mitosis and cell cycle exit, and ultimately results in premature neuronal differentiation. Additionally, we demonstrate that HIRA enhances β-catenin expression by recruiting H3K4 trimethyltransferase Setd1A, which increases H3K4me3 levels and heightens the promoter activity of β-catenin. Significantly, overexpression of HIRA, HIRA N-terminal domain, or β-catenin can override neurogenesis abnormities caused by HIRA defects. Collectively, these data implicate that HIRA, cooperating with Setd1A, modulates β-catenin expression and then regulates neurogenesis. This finding represents a novel epigenetic mechanism underlying the histone code and has profound and lasting implications for diseases and neurobiology.

Download Full-text

Nitric oxide acts in a positive feedback loop with BDNF to regulate neural progenitor cell proliferation and differentiation in the mammalian brain

Developmental Biology ◽

10.1016/s0012-1606(03)00120-9 ◽

2003 ◽

Vol 258 (2) ◽

pp. 319-333 ◽

Cited By ~ 209

Author(s):

Aiwu Cheng ◽

Shuqin Wang ◽

Jingli Cai ◽

Mahendra S Rao ◽

Mark P Mattson

Keyword(s):

Nitric Oxide ◽

Cell Proliferation ◽

Progenitor Cell ◽

Feedback Loop ◽

Neural Progenitor Cell ◽

Mammalian Brain ◽

Positive Feedback Loop ◽

Cell Proliferation And Differentiation ◽

Proliferation And Differentiation ◽

Progenitor Cell Proliferation

Download Full-text

Patched1–ArhGAP36–PKA–Inversin axis determines the ciliary translocation of Smoothened for Sonic Hedgehog pathway activation

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1804042116 ◽

2018 ◽

Vol 116 (3) ◽

pp. 874-879 ◽

Cited By ~ 11

Author(s):

Boyan Zhang ◽

Tenghan Zhuang ◽

Qiaoyu Lin ◽

Biying Yang ◽

Xiaowei Xu ◽

...

Keyword(s):

Cell Proliferation ◽

Sonic Hedgehog ◽

Initial Step ◽

Negative Regulator ◽

Individual Development ◽

Sonic Hedgehog Pathway ◽

Shh Pathway ◽

Pathway Activation ◽

Mother Centriole ◽

Signaling Activation

The Sonic Hedgehog (Shh) pathway conducts primarily in the primary cilium and plays important roles in cell proliferation, individual development, and tumorigenesis. Shh ligand binding with its ciliary membrane-localized transmembrane receptor Patched1 results in the removal of Patched1 from and the translocation of the transmembrane oncoprotein Smoothened into the cilium, leading to Shh signaling activation. However, how these processes are coupled remains unknown. Here, we show that the Patched1–ArhGAP36–PKA–Inversin axis determines the ciliary translocation of Smoothened. We find that Patched1 interacts with and stabilizes the PKA negative regulator ArhGAP36 to the centrosome. Activating the Shh pathway results in the removal of ArhGAP36 from the mother centriole and the centrosomal PKA accumulation. This PKA then phosphorylates Inversin and promotes its interaction with and the ciliary translocation of Smoothened. Knockdown of Inversin disrupts the ciliary translocation of Smoothened and Shh pathway activation. These findings reveal a regulatory molecular mechanism for the initial step of Shh pathway activation.

Download Full-text