Stefanakis Nikolaos, Xi Jasmine, Jiang Jessica, Shaham Shai
Laboratory of Developmental Genetics, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
Development. 2025 Jul 15;152(14). doi: 10.1242/dev.204622. Epub 2025 Jul 29.
Endothelial cells form the inner layer of blood vessels and play key roles in circulatory system development and function. A variety of endothelial cell types have been described through gene expression and transcriptome studies; nonetheless, the transcriptional programs that specify endothelial cell fate and maintenance are not well understood. To uncover such regulatory programs, we studied the C. elegans head mesodermal cell (HMC), a non-contractile mesodermal cell bearing molecular and functional similarities to vertebrate endothelial cells. Here, we demonstrate that a Forkhead transcription factor, LET-381, is required for HMC fate specification and maintenance of HMC gene expression. DMD-4, a DMRT transcription factor, acts downstream of and in conjunction with LET-381 to mediate these functions. Independently of LET-381, DMD-4 also represses the expression of genes associated with a different, non-HMC, mesodermal fate. Our studies uncover essential roles for FoxF transcriptional regulators in endothelial cell development and suggest that FoxF co-functioning target transcription factors promote specific non-contractile mesodermal fates.
内皮细胞构成血管的内层，在循环系统的发育和功能中发挥关键作用。通过基因表达和转录组研究已经描述了多种内皮细胞类型；然而，决定内皮细胞命运和维持其功能的转录程序仍未得到充分了解。为了揭示此类调控程序，我们研究了秀丽隐杆线虫的头部中胚层细胞（HMC），这是一种非收缩性中胚层细胞，在分子和功能上与脊椎动物内皮细胞相似。在此，我们证明叉头转录因子LET-381是HMC命运决定和HMC基因表达维持所必需的。DMRT转录因子DMD-4在LET-381的下游起作用，并与LET-381协同介导这些功能。独立于LET-381之外，DMD-4还抑制与另一种非HMC中胚层命运相关的基因的表达。我们的研究揭示了FoxF转录调节因子在内皮细胞发育中的重要作用，并表明FoxF共同作用的靶转录因子促进特定的非收缩性中胚层命运。
