ZFIN ID: ZDB-PUB-200403-200
Function of Arl4aa in the Initiation of Hematopoiesis in Zebrafish by Maintaining Golgi Complex Integrity in Hemogenic Endothelium
Guo, Y., Cheng, B.Y.L., Wang, D., Ma, A.C.H., He, B.L., Man, T.K., Cheung, M.P.L., Shi, X., Ng, N.K.L., Leung, A.Y.H.
Date: 2020
Source: Stem Cell Reports   14(4): 575-589 (Journal)
Registered Authors: Leung, Anskar
Keywords: Arl4aa, Golgi complex, Notch signaling, definitive hematopoietic stem cells, zebrafish
MeSH Terms:
  • Animals
  • Base Sequence
  • Conserved Sequence
  • Crosses, Genetic
  • Down-Regulation
  • Endothelial Cells/metabolism
  • Endothelial Cells/ultrastructure
  • Golgi Apparatus/metabolism*
  • Hemangioblasts/metabolism*
  • Hematopoiesis*
  • Humans
  • Models, Biological
  • Mutation/genetics
  • Receptors, Notch/metabolism
  • Signal Transduction
  • Transcription Activator-Like Effector Nucleases
  • Zebrafish/metabolism*
  • Zebrafish Proteins/metabolism*
PubMed: 32220330 Full text @ Stem Cell Reports
ADP-ribosylation factor-like 4aa (Arl4aa) is a member of the ADP-ribosylation factor family. It is expressed in hematopoietic tissue during embryonic development, but its function was unknown. Zebrafish arl4aa is preferentially expressed in the ventral wall of the dorsal aorta (VDA) at 24 and 36 hpf and in caudal hematopoietic tissue at 48 hpf. Morpholino knockdown and transcription activator-like effector nuclease (TALEN) knockout of arl4aa significantly reduced expression of genes associated with definitive hematopoietic stem cells (HSCs). Golgi complex integrity in VDA was disrupted as shown by transmission electron microscopy and immunostaining of Golgi membrane Giantin. Mechanistically, arl4aa knockdown reduced Notch signaling in the VDA and its target gene expression. Protein expression of NICD was also reduced. Effects of arl4aa knockdown on definitive hematopoiesis could be restored by NICD expression. This study identified arl4aa as a factor regulating initiation of definitive HSCs by maintaining the integrity of Golgi complex and, secondarily, maturation of the Notch receptor.