| First Author | Smart N | Year | 2010 |
| Journal | Nat Commun | Volume | 1 |
| Pages | 46 | PubMed ID | 20975697 |
| Mgi Jnum | J:186037 | Mgi Id | MGI:5430862 |
| Doi | 10.1038/ncomms1041 | Citation | Smart N, et al. (2010) Identification of Thymosin beta4 as an effector of Hand1-mediated vascular development. Nat Commun 1:46 |
| abstractText | The bHLH transcription factor Hand1 (Heart and neural crest-derived transcript-1) has a fundamental role in cardiovascular development; however, the molecular mechanisms have not been elucidated. In this paper we identify Thymosin beta4 (Tbeta4/Tmsb4x), which encodes an actin monomer-binding protein implicated in cell migration and angiogenesis, as a direct target of Hand1. We demonstrate that Hand1 binds an upstream regulatory region proximal to the promoter of Tbeta4 at consensus Thing1 and E-Box sites and identify both activation and repression of Tbeta4 by Hand1, through direct binding within either non-canonical or canonical E-boxes, providing new insight into gene regulation by bHLH transcription factors. Hand1-mediated activation of Tbeta4 is essential for yolk sac vasculogenesis and embryonic survival, and administration of synthetic TB4 partially rescues yolk sac capillary plexus formation in Hand1-null embryos. Thus, we identify an in vivo downstream target of Hand1 and reveal impaired yolk sac vasculogenesis as a primary cause of early embryonic lethality following loss of this critical bHLH factor. |
