RRC ID 66022
Author Rho SS, Kobayashi I, Oguri-Nakamura E, Ando K, Fujiwara M, Kamimura N, Hirata H, Iida A, Iwai Y, Mochizuki N, Fukuhara S.
Title Rap1b Promotes Notch-Signal-Mediated Hematopoietic Stem Cell Development by Enhancing Integrin-Mediated Cell Adhesion.
Journal Dev Cell
Abstract 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.
Volume 49(5)
Pages 681-696.e6
Published 2019-6-3
DOI 10.1016/j.devcel.2019.03.023
PII S1534-5807(19)30234-5
PMID 31006651
MeSH 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*
IF 10.092
Zebrafish itgb1b mi371