Differential Etv2 threshold requirement for endothelial and erythropoietic development

Cell Rep. 2022 May 31;39(9):110881. doi: 10.1016/j.celrep.2022.110881.


Endothelial and erythropoietic lineages arise from a common developmental progenitor. Etv2 is a master transcriptional regulator required for the development of both lineages. However, the mechanisms through which Etv2 initiates the gene-regulatory networks (GRNs) for endothelial and erythropoietic specification and how the two GRNs diverge downstream of Etv2 remain incompletely understood. Here, by analyzing a hypomorphic Etv2 mutant, we demonstrate different threshold requirements for initiation of the downstream GRNs for endothelial and erythropoietic development. We show that Etv2 functions directly in a coherent feedforward transcriptional network for vascular endothelial development, and a low level of Etv2 expression is sufficient to induce and sustain the endothelial GRN. In contrast, Etv2 induces the erythropoietic GRN indirectly via activation of Tal1, which requires a significantly higher threshold of Etv2 to initiate and sustain erythropoietic development. These results provide important mechanistic insight into the divergence of the endothelial and erythropoietic lineages.

Keywords: CP: Developmental biology; CP: Molecular biology; Etv2; GRN; Tal1; endothelial development; erythropoiesis; gene regulatory network; hematopoiesis; transcriptional regulation; yolk sac.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, N.I.H., Extramural

MeSH terms

  • Endothelium / metabolism
  • Gene Regulatory Networks*
  • Transcription Factors* / metabolism


  • Transcription Factors