Ectoderm to mesoderm transition by down-regulation of actomyosin contractility

Abstract

Collective migration of cohesive tissues is a fundamental process in morphogenesis and is particularly well illustrated during gastrulation by the rapid and massive internalization of the mesoderm, which contrasts with the much more modest movements of the ectoderm. In the Xenopus embryo, the differences in morphogenetic capabilities of ectoderm and mesoderm can be connected to the intrinsic motility of individual cells, very low for ectoderm, high for mesoderm. Surprisingly, we find that these seemingly deep differences can be accounted for simply by differences in Rho-kinases (Rock)-dependent actomyosin contractility. We show that Rock inhibition is sufficient to rapidly unleash motility in the ectoderm and confer it with mesoderm-like properties. In the mesoderm, this motility is dependent on two negative regulators of RhoA, the small GTPase Rnd1 and the RhoGAP Shirin/Dlc2/ArhGAP37. Both are absolutely essential for gastrulation. At the cellular and tissue level, the two regulators show overlapping yet distinct functions. They both contribute to decrease cortical tension and confer motility, but Shirin tends to increase tissue fluidity and stimulate dispersion, while Rnd1 tends to favor more compact collective migration. Thus, each is able to contribute to a specific property of the migratory behavior of the mesoderm. We propose that the “ectoderm to mesoderm transition” is a prototypic case of collective migration driven by a down-regulation of cellular tension, without the need for the complex changes traditionally associated with the epithelial-to-mesenchymal transition.

Distinct spatiotemporal contribution of morphogenetic events and mechanical tissue coupling during Xenopus neural tube closure

“…Our results indicate that the deep SE cells do not have a migratory capacity, in contrast with a previous study (Morita et al, 2012). These results agree both with the fact that deep ectoderm cells from gastrula embryos are not migratory (Kashkooli et al, 2021), and with the fact that SE explants developed up to tailbud stages never display any migratory behaviour. Using live imaging we show that the SE movement mirrors the movement of the NP, and its movement is directly influenced by NP morphogenesis.…”

“…However, this is in contrast with studies showing that excised NP explants can elongate and roll up ( Vijayraghavan and Davidson, 2017 ). Furthermore, the argument supporting an active movement of deep epidermal cells is inconsistent with the fact that that deep ectoderm cells from gastrula-stage embryos, unlike mesodermal cells, do not have the capacity to migrate when explanted from the embryo ( Kashkooli et al, 2021 ). In order to examine whether deep SE cells become migratory during neurulation and differ from their gastrula-stage counterparts, we explanted deep SE cells from stage 14 allowed them to attach to fibronectin (FN)-coated substrates and subsequently generated time-lapse recordings.…”

“…Dissections were performed in 1× MBSH [88 mM NaCl, 1 mM KCl, 2.4 mM NaHCO 3 , 0.82 mM MgSO 4 , 0.33 mM Ca (NO 3 ) 2 , 0.33 mM CaCl 2 , 10 mM HEPES and 10 μg/ml Streptomycin and Penicillin, pH 7.4). Single cells were dissociated in alkaline buffer (88 mM NaCl, 1 mM KCl and 10 mM NaHCO 3 , pH 9.5) as previously described ( Kashkooli et al, 2021 ). Dissociated cells were plated on FN-coated glass-bottom dishes and left to adhere for 45 min and then imaged.…”

Cell and Tissue Nanomechanics: From Early Development to Carcinogenesis

“…It was found that the ectoderm-to-mesoderm transition depends on the inhibition of ROCK signaling and the overexpression of Rnd1 and Shirin; these factors promote cell migration or mesodermal transition due to the downregulation of actomyosin contractility, which leads to the activation of the Hippo signaling pathway [ 118 ].…”

Engineering life in synthetic systems

“…François Fagotto (Montpellier Cell Biology Research Centre, Montpellier, France) explored how the Rho pathway controls cell stiffness during Xenopus gastrulation. He demonstrated that the downregulation of Rho kinases (Rock)-dependent actomyosin contractility triggers ectoderm-to-mesoderm transition (Kashkooli et al, 2021). Another paradigmatic example of drastic changes in cellular movements can be found during zebrafish development.…”