Tgfbr1regulates lateral plate mesoderm and endoderm reorganization during the trunk to tail transition

During the trunk to tail transition the mammalian embryo builds the outlets for the intestinal and urogenital tracts, lays down the primordia for the hindlimb and external genitalia, and switches from the epiblast/primitive streak to the tailbud as the driver of axial extension. Genetic and molecular data indicate thatTgfbr1is a key regulator of the trunk to tail transition.Tgfbr1has been shown to control the switch of the neuro mesodermal-competent cells from the epiblast to the chordo-neural hinge to generate the tail bud. We now show that Tgfbr1 signaling also controls the remodeling of the lateral plate mesoderm (LPM) and of the embryonic endoderm associated with the trunk to tail transition. In the absence ofTgfbr1the two LPM layers do not converge at the end of the trunk, extending instead as separate layers enclosing the celomic cavity until the caudal embryonic extremity, and failing to activate markers of primordia for the hindlimb and external genitalia. However, this extended LPM, does not exhibit the molecular signatures characteristic of this tissue in the trunk. The vascular remodeling involving the dorsal aorta and the umbilical artery leading to the connection between embryonic and extraembryonic circulation was also affected in theTgfbr1mutant embryos. Similar alterations in the LPM and vascular system were also observed inIsl1null mutants, indicating that this factor acts in the regulatory cascade downstream ofTgfbr1in LPM-derived tissues. In addition, in the absence ofTgfbr1the embryonic endoderm fails to expand to form the endodermal cloaca and to extend posteriorly to generate the tail gut. We present evidence suggesting that the remodeling activity ofTgfbr1in the LPM and endoderm results from the control of the posterior primitive streak fate after its regression during the trunk to tail transition. Our data, together with previously reported observations, placeTgfbr1at the top of the regulatory processes controlling the trunk to tail transition.