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

Yuhan Guo, Bowie Y.L. Cheng, Dandan Wang, Alvin C.H. Ma, Bai Liang He, Toni K. Man, May P.L. Cheung, Xiangguo Shi, Nelson K.L. Ng, Anskar Y.H. Leung

Research output: Journal article publicationJournal articleAcademic researchpeer-review

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.

Original languageEnglish
Pages (from-to)575-589
Number of pages15
JournalStem Cell Reports
Volume14
Issue number4
DOIs
Publication statusPublished - 14 Apr 2020
Externally publishedYes

Keywords

  • Arl4aa
  • definitive hematopoietic stem cells
  • Golgi complex
  • Notch signaling
  • zebrafish

ASJC Scopus subject areas

  • Biochemistry
  • Genetics
  • Developmental Biology
  • Cell Biology

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