Person: Lee, ChangHee
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ChangHee
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Lee, ChangHee
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Publication Molecular control of macroscopic forces drives formation of the vertebrate hindgut(Springer Science and Business Media LLC, 2019-01) Nerurkar, Nandan; Lee, ChangHee; Mahadevan, Lakshminarayanan; Tabin, CliffordThe embryonic gut tube is a cylindrical structure from which the respiratory and gastrointestinal tracts arise 1. Despite investigations into early emergence of the endoderm as an epithelial sheet 2,3 and later morphogenesis of the definitive digestive and respiratory organs 4–6, the intervening process of gut tube formation has been severely understudied, particularly over the past 45 years 7,8. Here we investigate the molecular control of macroscopic forces underlying early morphogenesis of the gut tube in the chick embryo. The gut tube has been described as forming from two endodermal invaginations – the Anterior Intestinal Portal (AIP) towards the rostral end of the embryo and the Caudal Intestinal Portal (CIP) at the caudal end – that migrate toward one another, internalizing the endoderm until they meet at the yolk stalk (umbilicus in mammals) 1,6. Migration of the AIP to form foregut has been descriptively characterized 9,10, yet the hindgut likely forms by a distinct mechanism that has not been fully elucidated 11. We find that the hindgut forms by collective cell movements through a stationary CIP, rather than via movement of the CIP itself. Moreover, combining in vivo imaging, biophysics, and mathematical modeling with molecular and embryological approaches, we identify a contractile force gradient that drives cell movements in the hindgut-forming endoderm, permitting tissue-scale posterior extension of the forming hindgut tube. The force gradient, in turn, is established in response to a morphogenic gradient of FGF signaling. As a result, we propose that an important positive feedback arises, whereby contracting cells draw passive cells from low to high FGF levels, recruiting them to contract and pull more cells into the elongating hindgut. In addition to providing new insight into the early gut development, these findings illustrate how large-scale tissue level forces can be traced to developmental signals during vertebrate morphogenesis.