PUBLICATION

Function of Arl4aa in the Initiation of Hematopoiesis in Zebrafish by Maintaining Golgi Complex Integrity in Hemogenic Endothelium

Authors
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.
ID
ZDB-PUB-200403-200
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
Abstract
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.
Genes / Markers
Figures
Show all Figures
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes