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 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 through a Notch signaling independent manner. We show that D1ICD 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 via modulating not only Notch signaling but also the MAP kinase pathway.
Cleaved Delta like 1 intracellular domain regulates neural development via Notch signal dependent and independent pathways
Present address: Division of Cellular and Molecular Toxicology, Center for Biological Safety & Research, National Institute of Health Sciences, 3-25-26, Kawasaki-ku Tonomachi, Kawasaki, Kanagawa 210-9501, Japan
- Award Group:
- Funder(s): Japan Society for the Promotion of Science
- Award Id(s): 25840096
- Funder(s):
- Award Group:
- Funder(s): Takeda Science Foundation
- Funder(s):
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Yusuke Okubo, Fumiaki Ohtake, Katsuhide Igarashi, Yukuto Yasuhiko, Yoko Hirabayashi, Yumiko Saga, Jun Kanno; Cleaved Delta like 1 intracellular domain regulates neural development via Notch signal dependent and independent pathways. Development 2021; dev.193664. doi: https://doi.org/10.1242/dev.193664
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