Matrix adhesion polarizes heart progenitor induction in the invertebrate chordate Ciona intestinalis

Abstract

SUMMARYCell-matrix adhesion strongly influences developmental signaling. Resulting impacts on cell migration and tissue morphogenesis are well characterized. However, the in vivo impact of adhesion on fate induction remains ambiguous. Here, we employ the invertebrate chordate Ciona intestinalis to delineate an essential in vivo role for matrix adhesion in heart progenitor induction. In Ciona precardiac founder cells, invasion of the underlying epidermis promotes localized induction of the heart progenitor lineage. We found that these epidermal invasions are associated with matrix adhesion along the pre-cardiac cell/epidermal boundary. Through targeted manipulations of RAP GTPase activity, we were able to manipulate pre-cardiac cell-matrix adhesion. Targeted disruption of precardiac cell-matrix adhesion blocked heart progenitor induction. Conversely, increased matrix adhesion generated expanded induction. We were also able to selectively restore cell-matrix adhesion and heart progenitor induction through targeted expression of CiIntegrin β2. These results indicate that matrix adhesion functions as a necessary and sufficient extrinsic cue for regional heart progenitor induction. Furthermore, time-lapse imaging suggests that cytokinesis acts as an intrinsic temporal regulator of heart progenitor adhesion and induction. Our findings highlight a potentially conserved role for matrix adhesion in early steps of vertebrate heart progenitor specification.

Surrounding tissues canalize motile cardiopharyngeal progenitors towards collective polarity and directed migration

“…Studies indicated that the cardiopharyngeal founder cells are exposed to a uniform distribution of FGF ligands and that TVC induction occurs via asymmetrical integrin-mediated adhesion with the epidermis (Cooley et al, 2011;Norton et al, 2013). These studies indicated that both TVCs are induced by essentially the same mechanism.…”

“…The TVCs are born contacting the ventral epidermis (Nishida, 1987;Nishida and Satoh, 1985) and establish integrin-mediated adhesion to the epidermal extracellular matrix, which is required for TVC specification by polarizing sustained MAPK activity (Cooley et al, 2011;Norton et al, 2013). During their migration, TVCs maintain contact with the posterior trunk epidermis (Nishida, 1987;Nishida and Satoh, 1985).…”

“…The leader forms more prominent protrusions than the trailer, which abuts it and has a constricted trailing end (supplementary material Movie 1; Christiaen et al, 2008). Additionally, TVCs maintain cadherin-based cell-cell adhesion throughout migration (Norton et al, 2013). The Ciona cardiogenic lineage arises from a single pair of blastomeres called B7.5, which divide twice during gastrulation, giving rise to pairs of smaller anterior cardiogenic progenitors (trunk ventral cells, TVCs) and larger posterior anterior tail muscles (ATMs; supplementary material Fig.…”

Mitotic Membrane Turnover Coordinates Differential Induction of the Heart Progenitor Lineage

“…In vitro studies have also revealed that matrix adhesion can profoundly influence growth factor signaling thereby impacting stem cell fate specification (Dave et al, 2014;Engler et al, 2006;Reilly and Engler, 2010;Yim and Sheetz, 2012). In contrast, relatively few studies have focused on the role of matrix adhesion in embryonic cell specification (Miller and Davidson., 2013;Brunet et al, 2013;Farge, 2011;Fonar et al, 2011;Martin-Bermudo, 2000;Norton et al, 2013). Thus, the dynamic, in vivo impact of matrix adhesion on embryonic cell fate decisions remains poorly characterized.…”

“…Previous work has revealed a key role for matrix adhesion in differential heart progenitor induction ( Figure 1A 0 ). Prior to division, founder cells exhibit a broad domain of matrix adhesion along the ventral, epidermal boundary (Norton et al, 2013). This adherent domain correlates with a broad region of FGF receptor activation.…”