Pcdh18a regulates endocytosis of E-cadherin during axial mesoderm development in zebrafish

Abstract

The notochord defines the axial structure of all vertebrates during development. Notogenesis is a result of major cell reorganization in the mesoderm, the convergence and the extension of the axial cells. However, it is currently not fully understood how these processes act together in a coordinated way during notochord formation. The prechordal plate is an actively migrating cell population in the central mesoderm anterior to the trailing notochordal plate cells. We show that prechordal plate cells express Protocadherin 18a (Pcdh18a), a member of the cadherin superfamily. We find that Pcdh18a-mediated recycling of E-cadherin adhesion complexes transforms prechordal plate cells into a cohesive and fast migrating cell group. In turn, the prechordal plate cells subsequently instruct the trailing mesoderm. We simulated cell migration during early mesoderm formation using a lattice-based mathematical framework and predicted that the requirement for an anterior, local motile cell cluster could guide the intercalation and extension of the posterior, axial cells. Indeed, a grafting experiment validated the prediction and local Pcdh18a expression induced an ectopic prechordal plate-like cell group migrating towards the animal pole. Our findings indicate that the Pcdh18a is important for prechordal plate formation, which influences the trailing mesodermal cell sheet by orchestrating the morphogenesis of the notochord.

A dual involvement of Protocadherin 18a in stromal cell development guides the formation of a functional hematopoietic niche

“…To investigate the possible involvement of Pcdh18a in SCP emigration from the somites, we firstly used an antisense morpholino (MO). Previous studies found that morpholinos blocking Pcdh18a translation caused defects in the early development of zebrafish embryos and lethality by mid-somitogenesis (Aamar and Dawid, 2008;Bosze et al, 2020). We found that a splice-blocking MO targeting the intron1-exon2 (i1e2) junction of nascent pcdh18a RNA led with high efficiency to retention of intron 1 in the mRNA (Fig.…”

Guidance by followers ensures long-range coordination of cell migration through α-Catenin mechanoperception

“…A question remains however: what is driving the movement of following cells? It was recently established that a group of cells, located just posterior to the polster, expresses pcdh18a , which, by modulating E-cadherin recycling, would transform them into a fast-migrating group (Bosze et al, 2020) which represents an attractive candidate to guide polster migration. If true, this, however, only shifts the question to how these cells are oriented towards the animal pole.…”

JNK Mediates Differentiation, Cell Polarity and Apoptosis During Amphioxus Development by Regulating Actin Cytoskeleton Dynamics and ERK Signalling

“…Despite several differences with vertebrate anatomy and genoarchitecture, this six3/6 + region may represent the amphioxus homologue of the prechordal plate (Albuixech-Crespo et al, 2017). In vertebrates, notochord formation from axial mesoderm requires the complex orchestration among active migration of prechordal cells (Bosze et al, 2020), non-canonical Wnt11-mediated cellular movements of paraxial mesoderm (Heisenberg et al, 2000), and CE of deep neural cells (Keller and Sutherland, 2020). Treatment with SP600125 also inhibits the mediolateral cell intercalation of the neurectoderm required for axial elongation in the annelid Platynereis dumerilii (Steinmetz et al, 2007).…”