Apical constriction and epithelial invagination are regulated by BMP activity

Abstract

Epithelial invagination is a morphological process in which flat cell sheets transform into three-dimensional structures through bending of the tissue. It is accompanied by apical constriction, in which the apical cell surface is reduced in relation to the basal cell surface. Although much is known about the intra-cellular molecular machinery driving apical constriction and epithelial invagination, information of how extra-cellular signals affect these processes remains insufficient. In this study we have established several in vivo assays of placodal invagination to explore whether the external signal BMP regulates processes connected to epithelial invagination. By inhibiting BMP activity in prospective cranial placodes, we provide evidence that BMP signals are required for RhoA and F-actin rearrangements, apical constriction, cell elongation and epithelial invagination. The failure of placode invagination after BMP inhibition appears to be a direct consequence of disrupted apical accumulation of RhoA and F-actin, rather than changes in cell death or proliferation. In addition, our results show that epithelial invagination and acquisition of placode-specific identities are two distinct and separable developmental processes. In summary, our results provide evidence that BMP signals promote epithelial invagination by acting upstream of the intracellular molecular machinery that drives apical constriction and cell elongation.

Signaling and Gene Regulatory Networks in Mammalian Lens Development

“…This contact is established by the constraining effects of ECM [123] and the formation of F-actin-rich basal temporal filopodia acting as physical tethers [124]. This model was further extended by findings which showed that the ECM causes lens cells to thicken locally in order to facilitate subsequent invagination [99, 125], a process primarily driven by both apical constriction to produce wedge-shaped cells [122, 126] and by BMP signaling [127]. In the invaginating lens placode, the cells near the lens pit circumferentially contract the adherens junctional complexes joining them together, and this actomyosin cytoskeleton remodeling requires RhoA small GTPase, Rho-kinase (Rock), PDZ domain-containing protein Shroom3, and p120-catenin δ1 [122, 126].…”

Cellular systems for epithelial invagination

“…For instance, Rho GTPase [17] and p120 catenin [13] are required to localize myosin II apically in the cell. BMP, acting upstream of Rock in chick otic placode (neuroepithelial) invagination, seems to be required for apical localization of actin independently of a role in cell type specification [23].

Figure 1.Classical apical constriction.

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Actomyosin dynamics, Bmp and Notch signaling pathways drive apical extrusion of proepicardial cells

“…Another possibility is that Bmp2 rescues the F-actin tension by modulating the expression of other non-conventional myosins that are not inhibited by BDM. Indeed, Bmp signaling has been recently shown to regulate epithelial morphogenesis by controlling F-actin rearrangements, apical constriction, cell elongation and epithelial bending 78 . Along this line, interkinetic nuclear migration during morphogenesis of the retina is driven by actomyosin forces that are blocked when myosin II is inhibited, and the reduction in the velocity of migration and cytoskeleton dynamics by BDM can be rescued by BDM-insensitive myosins 79 .…”