Sonic Hedgehog Regulates Integrin Activity, Cadherin Contacts, and Cell Polarity to Orchestrate Neural Tube Morphogenesis

Abstract

In vertebrates, the embryonic nervous system is shaped and patterned by a series of temporally and spatially regulated cell divisions, cell specifications, and cell adhesions and movements. Morphogens of the Hedgehog, Wnt, and bone morphogenetic protein families have been shown to play a crucial role in the control of cell division and specification in the trunk neural tube, but their possible implication in the regulation of adhesive events has been poorly documented. In the present study, we demonstrate that Sonic hedgehog regulates neural epithelial cell adhesion and polarity through regulation of integrin activity, cadherin cell-cell contact, and cell polarity genes in immature neural epithelial cells before the specification of neuronal cells. We propose that Sonic hedgehog orchestrates neural tube morphogenesis by coordinating adhesive and motility events with cell proliferation and differentiation.

Atypical protein kinase C (aPKCζ and aPKCλ) is dispensable for mammalian hematopoietic stem cell activity and blood formation

“…In other model systems, asymmetric cell division is preceded by the activation of the aPKCζ-Par6-Par3 polarity complex and the realignment of the microtubule cytoskeleton (7,11). We analyzed the distribution of aPKCζ and Par6 in WT HSCs in vitro after overnight culture on fibronectin, a major component of the hematopoietic microenvironment, which is responsible for integrin polarization and signaling (35). Although the intracellular locali- zation of tubulin, a major constituent of the microtubular network, was highly polarized in isolated HSCs, which were in contact with fibronectin, the distribution of aPKCζ and Par6 was not proportional to the frequency of tubulin polarized HSCs (Fig.…”

Diversity in the molecular and cellular strategies of epithelium-to-mesenchyme transitions: Insights from the neural crest

“…This is consistent with the fact that epithelial cells, thereby limiting their migratory capacities. 221,222 The EMT capacity of neural epithelial cells has been evaluated directly on neural tube fragments collected at different stages of neurulation and explanted in vitro under conditions free of the environmental influences and physical constraints present in the embryo. 142 Although neural epithelial cells show the ability to spread on the dish and migrate as a sheet during the initial stages of neurulation, they fail to undergo EMT even after prolonged cultures.…”

“…For example, electroporation of Ets-1 or HIP-1, an antagonist of Shh signals, results in massive cell delamination in the neural tube without induction of Sox-10 or HNK-1 markers. 55,222 Of interest, in these experiments, cells lose their epithelial structure, but they fail to migrate at distance from the neural tube and generally remain anchored to the neural epithelium or die, indicating that acquisition of NC cell traits is critical for complete delamination and efficient migration and survival.…”

Stable, conditional, and muscle‐fiber‐specific expression of electroporated transgenes in chick limb muscle cells

“…Electroporation is a well-established method of gene transfer into neural and mesodermal tissues in chick embryos. Multiple functional studies based on somite and neural tube electroporation have been published (Delfini and Duprez, 2004;Gros et al, 2004Gros et al, , 2009Fournier-Thibault et al, 2009;Osorio et al, 2009). Recently, a gene transfer system by electroporation into aortic endothelial cell has been reported (Rossello and Torres, 2010).…”