ZFIN ID: ZDB-PUB-200422-79
Rab5c-mediated endocytic trafficking regulates hematopoietic stem and progenitor cell development via Notch and AKT signaling
Heng, J., Lv, P., Zhang, Y., Cheng, X., Wang, L., Ma, D., Liu, F.
Date: 2020
Source: PLoS Biology   18: e3000696 (Journal)
Registered Authors: Liu, Feng, Lv, Peng, Ma, Dongyuan, Zhang, Yifan
Keywords: none
MeSH Terms:
  • Animals
  • Animals, Genetically Modified
  • Embryo, Nonmammalian
  • Endocytosis
  • Endothelium/physiology
  • Gene Expression Regulation, Developmental
  • HEK293 Cells
  • Hematopoietic Stem Cells/physiology*
  • Humans
  • Proto-Oncogene Proteins c-akt/metabolism*
  • Receptors, Notch/genetics
  • Receptors, Notch/metabolism*
  • T-Box Domain Proteins/genetics
  • T-Box Domain Proteins/metabolism
  • Transcription Factors/genetics
  • Zebrafish/embryology
  • Zebrafish/genetics
  • Zebrafish/metabolism
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
  • rab5 GTP-Binding Proteins/chemistry
  • rab5 GTP-Binding Proteins/genetics
  • rab5 GTP-Binding Proteins/metabolism*
PubMed: 32275659 Full text @ PLoS Biol.
It is well known that various developmental signals play diverse roles in hematopoietic stem and progenitor cell (HSPC) production; however, how these signaling pathways are orchestrated remains incompletely understood. Here, we report that Rab5c is essential for HSPC specification by endocytic trafficking of Notch and AKT signaling in zebrafish embryos. Rab5c deficiency leads to defects in HSPC production. Mechanistically, Rab5c regulates hemogenic endothelium (HE) specification by endocytic trafficking of Notch ligands and receptor. We further show that the interaction between Rab5c and Appl1 in the endosome is required for the survival of HE in the ventral wall of the dorsal aorta through AKT signaling. Interestingly, Rab5c overactivation can also lead to defects in HSPC production, which is attributed to excessive endolysosomal trafficking inducing Notch signaling defect. Taken together, our findings establish a previously unrecognized role of Rab5c-mediated endocytic trafficking in HSPC development and provide new insights into how spatiotemporal signals are orchestrated to accurately execute cell fate transition.