Iacolare Olimpia, Ferrentino Rosa, Altomonte Alessandra, Turner Christopher E, Baldini Antonio, Alfano Daniela
Institute of Genetics and Biophysics Adriano Buzzati-Traverso, National Research Council, Naples, Italy.
Department of Cell and Developmental Biology, SUNY Upstate Medical University, Syracuse, NY, USA.
Life Sci Alliance. 2025 May 29;8(8). doi: 10.26508/lsa.202403151. Print 2025 Aug.
The T-box transcription factor TBX1 is expressed in the cardio-pharyngeal mesoderm. The correct cell fate decisions of cardio-pharyngeal mesoderm cells are critical, as any defect in this process can alter second heart field morphogenesis and lead to cardiac outflow tract and pharyngeal apparatus defects. The second heart field plays a crucial role in cardiac development by incorporating cardiac progenitors into the heart. It is also the major gene implicated in 22q11.2 deletion (or DiGeorge) syndrome, a primary genetic cause of congenital heart defects associated with hypoplasia of the cardiac outflow tract. The murine model recapitulates the heart phenotype and shows anomalies in the ECM-integrin-focal adhesion pathway. Here, we used a cell culture model to manipulate levels in order to molecularly and functionally characterize the defective focal adhesions (FAs) caused by loss and to analyse their dynamics on the ECM. Intriguingly, we found that regulates FA dynamics by influencing the FA disassembly process. Furthermore, is required for the paxillin (PXN) signalling pathway and controls cell spreading primarily through regulation. In fact, consistent with this observation, the ectopic expression of PXN rescued the cell spreading and signalling defects caused by depletion. Finally, our study revealed that, at least in vitro, TBX1 is a critical regulator of cell adhesion by affecting FA turnover.
T盒转录因子TBX1在心咽中胚层中表达。心咽中胚层细胞正确的细胞命运决定至关重要，因为这一过程中的任何缺陷都可能改变第二心脏场形态发生，并导致心脏流出道和咽器官缺陷。第二心脏场通过将心脏祖细胞纳入心脏，在心脏发育中起关键作用。它也是与22q11.2缺失（或DiGeorge）综合征相关的主要基因，22q11.2缺失综合征是先天性心脏缺陷的主要遗传原因，与心脏流出道发育不全有关。小鼠模型重现了心脏表型，并显示出细胞外基质-整合素-粘着斑途径的异常。在这里，我们使用细胞培养模型来操纵[具体物质]水平，以便从分子和功能上表征由[具体物质]缺失导致的缺陷粘着斑（FAs），并分析它们在细胞外基质上的动态变化。有趣的是，我们发现[具体物质]通过影响粘着斑的拆卸过程来调节粘着斑动态变化。此外，[具体物质]是桩蛋白（PXN）信号通路所必需的，并且主要通过[具体调节方式]来控制细胞铺展。事实上，与这一观察结果一致，PXN的异位表达挽救了由[具体物质]耗竭引起的细胞铺展和信号缺陷。最后，我们的研究表明，至少在体外，TBX1通过影响粘着斑周转是细胞粘附的关键调节因子。
