ZFIN ID: ZDB-PUB-190423-3
Rap1b Promotes Notch-Signal-Mediated Hematopoietic Stem Cell Development by Enhancing Integrin-Mediated Cell Adhesion
Rho, S.S., Kobayashi, I., Oguri-Nakamura, E., Ando, K., Fujiwara, M., Kamimura, N., Hirata, H., Iida, A., Iwai, Y., Mochizuki, N., Fukuhara, S.
Date: 2019
Source: Developmental Cell   49(5): 681-696.e6 (Journal)
Registered Authors: Fukuhara, Shigetomo, Hirata, Hiromi, Kobayashi, Isao, Mochizuki, Naoki
Keywords: Notch, Rap1, fibronectin, hematopoietic stem cell, hemogenic endothelium, integrin β1, migration, posterior lateral plate mesoderm, somite, zebrafish
MeSH Terms:
  • Animals
  • Cell Adhesion*
  • Fibronectins/genetics
  • Fibronectins/metabolism*
  • Hematopoietic Stem Cells/cytology*
  • Hematopoietic Stem Cells/metabolism
  • Integrin beta1/genetics
  • Integrin beta1/metabolism*
  • Receptors, Notch/genetics
  • Receptors, Notch/metabolism*
  • Zebrafish
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
  • rap GTP-Binding Proteins/genetics
  • rap GTP-Binding Proteins/metabolism*
PubMed: 31006651 Full text @ Dev. Cell
Hematopoietic stem cells (HSCs) emerge from hemogenic endothelium (HE) within the ventral portion of the dorsal aorta during vertebrate development. In zebrafish, Notch signaling induces HE specification from posterior lateral plate mesoderm (PLPM) cells as they migrate over the ventral surface of the somite. During migration, PLPM cells make close contact with Notch-ligand-expressing somitic cells to acquire HE identity. Herein, we show in zebrafish that the small GTPase Rap1b regulates HSC development by potentiating Notch-mediated HE specification. PLPM cells migrate toward the midline along the somite boundary where fibronectin accumulates. Rap1b stimulates integrin β1 to enhance PLPM cell adhesion to fibronectin localized at the somite boundary. Rap1b-induced integrin-β1-mediated adhesion to fibronectin leads to the spreading of PLPM cells to facilitate their physical contact with the Notch-ligand-expressing somitic cells, thereby promoting Notch-mediated HE specification. Thus, we have revealed an unexpected role of Rap1-induced integrin-mediated cell adhesion in HSC development.