Powell Olivia, Garcia Emily, Sriram Vanshika, Qu Yi, Nerurkar Nandan L
Department of Biomedical Engineering, Columbia University, New York NY 10027.
bioRxiv. 2024 Nov 1:2024.10.31.621372. doi: 10.1101/2024.10.31.621372.
The foregut tube gives rise to the lungs and upper gastrointestinal tract, enabling vital functions of respiration and digestion. How the foregut tube forms during embryonic development has historically received considerable attention, but over the past few decades this question has primarily been addressed indirectly through studies on morphogenesis of the primitive heart tube, a closely related process. As a result, many aspects of foregut development remain unresolved. Here, we exploit the accessibility of the chick embryo to study the initial formation of the foregut tube, combining embryology with fate mapping, live imaging, and biomechanical analyses. The present study reveals that the foregut forms and elongates over a narrower time window than previously thought, and displays marked dorso-ventral and left-right asymmetries early in its development. Through tissue-specific ablation of endoderm along the anterior intestinal portal, we confirm its central biomechanical role in driving foregut morphogenesis, despite not directly contributing cells to the elongating tube. We further confirm the important role of this cell population in formation of the heart tube, with evidence that this role extends to later stages of cardiac looping as well. Together, these data reveal the need for an intricate balance between intrinsic cell behaviors and extrinsic forces for normal foregut elongation, and set the stage for future studies aimed at understanding the underlying molecular cues that coordinate this balance.
前肠管发育形成肺和上消化道,实现呼吸和消化等重要功能。前肠管在胚胎发育过程中如何形成,长期以来一直备受关注,但在过去几十年里,这个问题主要是通过对原始心管形态发生的研究间接解决的,原始心管形态发生是一个与之密切相关的过程。因此,前肠发育的许多方面仍未得到解决。在这里,我们利用鸡胚易于研究的特点,结合胚胎学、命运图谱、实时成像和生物力学分析,来研究前肠管的初始形成。本研究表明,前肠的形成和伸长所经历的时间窗口比以前认为的更窄,并且在其发育早期就表现出明显的背腹和左右不对称性。通过沿前肠门对特定组织的内胚层进行消融,我们证实了内胚层在驱动前肠形态发生中的核心生物力学作用,尽管它并不直接为伸长的前肠管提供细胞。我们进一步证实了这群细胞在心脏管形成中的重要作用,有证据表明这种作用也延伸到心脏环化的后期阶段。总之,这些数据揭示了正常前肠伸长需要内在细胞行为和外在力量之间的复杂平衡,并为未来旨在理解协调这种平衡的潜在分子线索的研究奠定了基础。