| First Author | Sinha T | Year | 2022 |
| Journal | Cell Rep | Volume | 39 |
| Issue | 9 | Pages | 110881 |
| PubMed ID | 35649376 | Mgi Jnum | J:326086 |
| Mgi Id | MGI:7294034 | Doi | 10.1016/j.celrep.2022.110881 |
| Citation | Sinha T, et al. (2022) Differential Etv2 threshold requirement for endothelial and erythropoietic development. Cell Rep 39(9):110881 |
| abstractText | 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. |
