Cleaved Delta like 1 intracellular domain regulates neural development via Notch signal-dependent and -independent pathways

被引：4

作者：

Okubo, Yusuke ^{[1
,6
]}

Ohtake, Fumiaki ^{[1
,2
]}

Igarashi, Katsuhide ^{[1
,3
]}

Yasuhiko, Yukuto ^{[1
,6
]}

Hirabayashi, Yoko ^{[1
,6
]}

Saga, Yumiko ^{[4
,5
]}

Kanno, Jun ^{[1
,6
]}

机构：

[1] Natl Inst Hlth Sci, Ctr Biol Safety & Res, Div Cellular & Mol Toxicol, Setagaya Ku, 1-18-1 Kamiyoga, Tokyo 1588501, Japan

[2] Hoshi Univ, Inst Adv Life Sci, Shinagawa Ku, 2-4-41 Ebara, Tokyo 1428501, Japan

[3] Hoshi Univ, Life Sci Tokyo Adv Res Ctr L StaR, Sch Pharm & Pharmaceut Sci, Shinagawa Ku, 2-4-41 Ebara, Tokyo 1428501, Japan

[4] Natl Inst Genet, Div Mammalian Dev, Yata 1111, Mishima, Shizuoka 4118540, Japan

[5] Univ Tokyo, Grad Sch Sci, Dept Biol Sci, Bunkyo Ku, Hongo 7-3-1, Tokyo 1130033, Japan

[6] Natl Inst Hlth Sci, Ctr Biol Safety & Res, Div Cellular & Mol Toxicol, Kawasaki Ku, 3-25-26 Tonomachi, Kawasaki, Kanagawa 2109501, Japan

来源：

DEVELOPMENT | 2021年 / 148卷 / 19期

基金：

日本学术振兴会;

关键词：

Delta-like 1 intracellular domain; Notch signaling; DRG development; Lateral inhibition; Map kinase pathway; LIGAND DELTA1; CELLS; NUMB; NEUROGENESIS; DEGRADATION; INHIBITION; SECRETASE; PROTEINS; DELETION; BINDING;

D O I：

10.1242/dev.193664

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Notch-Delta signaling regulates many developmental processes, including tissue homeostasis and maintenance of stem cells. Upon interaction of juxtaposed cells via Notch and Delta proteins, intracellular domains of both transmembrane proteins are cleaved and translocate to the nucleus. Notch intracellular domain activates target gene expression; however, the role of the Delta intracellular domain remains elusive. Here, we show the biological function of Delta like 1 intracellular domain (D1ICD) by modulating its production. We find that the sustained production of D1ICD abrogates cell proliferation but enhances neurogenesis in the developing dorsal root ganglia (DRG), whereas inhibition of D1ICD production promotes cell proliferation and gliogenesis. D1ICD acts as an integral component of lateral inhibition mechanism by inhibiting Notch activity. In addition, D1ICD promotes neurogenesis in a Notch signaling-independent manner. We show that DlICD binds to Erk1/2 in neural crest stem cells and inhibits the phosphorylation of Erk1/2. In summary, our results indicate that D1ICD regulates DRG development by modulating not only Notch signaling but also the MAP kinase pathway.

引用

页数：12

共 40 条

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