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.

中文翻译：

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Pitx2 通过潜在的 TGFβ 模拟油门刹车机械反馈来旋转肠道

脊椎动物的肠道是由不对称的肠道旋转和伸长形成的，错误会导致人类婴儿出现致命的梗阻。旋转始于背侧肠系膜的组织变形，这取决于成对样转录因子的左侧表达Pitx2. 保守的形态发生素节点诱发不对称Pitx2控制胚胎的偏侧性，但器官水平的调节Pitx2在肠道不对称期间仍然未知。我们发现节点可有可无Pitx2肠系膜变形过程中的表达。肠道旋转需要一种机械敏感的潜在转化生长因子-β (TGFβ)，调整第二波Pitx2作为与右侧的机械反馈，在左侧肠系膜中引起相互组织僵硬。这种信号调节器，一个加速器（右）和一个制动器（左），结合生化和生物力学输入来打破肠道形态对称性和引导肠道旋转。