研究人员发现，在肠系膜变形过程中，Nodal对Pitx2的表达是不需要的。肠道旋转反而需要一个机械敏感的潜在的转化生长因子-β（TGFβ），调整Pitx2的第二波，并作为与右侧的机械反馈，诱导左侧肠系膜响应的组织硬度。这种信号调节器是一个加速器（右）和制动器（左），它结合了生化和生物力学输入，打破了肠道形态对称性并指导肠道旋转。
据了解，脊椎动物的肠道是通过不对称的肠道旋转和伸长形成的，错误会导致人类婴儿的致命性梗阻。旋转始于背侧肠系膜的组织变形，这取决于左侧的类Pitx2转录因子表达。保守的形态发生因子Nodal诱导不对称的Pitx2来管理胚胎的侧向性，但在肠道不对称过程中Pitx2的器官水平调节仍然是未知的。
附：英文原文
Title: Pitx2 patterns an accelerator-brake mechanical feedback through latent TGFβ to rotate the gut
Author: Bhargav D. Sanketi, Noam Zuela-Sopilniak, Elizabeth Bundschuh, Sharada Gopal, Shing Hu, Joseph Long, Jan Lammerding, Sevan Hopyan, Natasza A. Kurpios
Issue&Volume: 2022-09-23
Abstract: The vertebrate intestine forms by asymmetric gut rotation and elongation, and errors cause lethal obstructions in human infants. Rotation begins with tissue deformation of the dorsal mesentery, which is dependent on left-sided expression of the Paired-like transcription factor Pitx2. The conserved morphogen Nodal induces asymmetric Pitx2 to govern embryonic laterality, but organ-level regulation of Pitx2 during gut asymmetry remains unknown. We found Nodal to be dispensable for Pitx2 expression during mesentery deformation. Intestinal rotation instead required a mechanosensitive latent transforming growth factor–β (TGFβ), tuning a second wave of Pitx2 that induced reciprocal tissue stiffness in the left mesentery as mechanical feedback with the right side. This signaling regulator, an accelerator (right) and brake (left), combines biochemical and biomechanical inputs to break gut morphological symmetry and direct intestinal rotation.
DOI: abl3921
Source: https://www.science.org/doi/10.1126/science.abl3921