Lozovska Anastasiia, Casaca Ana, Novoa Ana, Kuo Ying-Yi, Jurberg Arnon D, Martins Gabriel G, Hadjantonakis Anna-Katerina, Mallo Moises
Instituto Gulbenkian de Ciência, Rua da Quinta Grande, Oeiras, Portugal.
Gulbenkian Institute for Molecular Medicine, Avenida Prof. Egas Moniz, Lisboa, Portugal.
Elife. 2025 Jan 28;13:RP94290. doi: 10.7554/eLife.94290.
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 (PS) to the tail bud as the driver of axial extension. Genetic and molecular data indicate that Tgfbr1 is a key regulator of the trunk to tail transition. Tgfbr1 has been shown to control the switch of the neuromesodermal competent cells from the epiblast to the chordoneural hinge to generate the tail bud. We now show that in mouse embryos 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 of Tgfbr1, the two LPM layers do not converge at the end of the trunk, extending instead as separate layers until the caudal embryonic extremity, and failing to activate markers of primordia for the hindlimb and external genitalia. The vascular remodeling involving the dorsal aorta and the umbilical artery leading to the connection between embryonic and extraembryonic circulation was also affected in the Tgfbr1 mutant embryos. Similar alterations in the LPM and vascular system were also observed in Isl1 null mutants, indicating that this factor acts in the regulatory cascade downstream of Tgfbr1 in LPM-derived tissues. In addition, in the absence of Tgfbr1 the 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 of Tgfbr1 in the LPM and endoderm results from the control of the posterior PS fate after its regression during the trunk to tail transition. Our data, together with previously reported observations, place Tgfbr1 at the top of the regulatory processes controlling the trunk to tail transition.
在从躯干向尾部过渡的过程中，哺乳动物胚胎构建了肠道和泌尿生殖道的出口，奠定了后肢和外生殖器的原基，并从外胚层/原条（PS）转变为尾芽作为轴向延伸的驱动因素。遗传和分子数据表明，Tgfbr1是从躯干向尾部过渡的关键调节因子。已证明Tgfbr1可控制神经中胚层能干细胞从外胚层向脊神经铰链的转变，以生成尾芽。我们现在表明，在小鼠胚胎中，Tgfbr1信号传导还控制与从躯干向尾部过渡相关的侧板中胚层（LPM）和胚胎内胚层的重塑。在缺乏Tgfbr1的情况下，两个LPM层在躯干末端不会汇合，而是作为单独的层延伸至胚胎尾端，并且无法激活后肢和外生殖器原基的标志物。涉及背主动脉和脐动脉的血管重塑，从而导致胚胎循环与胚外循环之间的连接，在Tgfbr1突变胚胎中也受到影响。在Isl1基因敲除突变体中也观察到LPM和血管系统的类似改变，表明该因子在源自LPM的组织中Tgfbr1下游的调节级联中起作用。此外，在缺乏Tgfbr1的情况下，胚胎内胚层无法扩展以形成内胚层泄殖腔，也无法向后延伸以生成尾肠。我们提供的证据表明，Tgfbr1在LPM和内胚层中的重塑活性源于其在从躯干向尾部过渡期间退化后对后PS命运的控制。我们的数据与先前报道的观察结果一起，将Tgfbr1置于控制从躯干向尾部过渡的调节过程的顶端。
