Wnt signaling balances specification of the cardiac and pharyngeal muscle fields

Abstract

Canonical Wnt/β-catenin (Wnt) signaling plays multiple conserved roles during fate specification of cardiac progenitors in developing vertebrate embryos. Although lineage analysis in ascidians and mice has indicated there is a close relationship between the cardiac second heart field (SHF) and pharyngeal muscle (PM) progenitors, the signals underlying directional fate decisions of the cells within the cardio-pharyngeal muscle field in vertebrates are not yet understood. Here, we examined the temporal requirements of Wnt signaling in cardiac and PM development. In contrast to a previous report in chicken embryos that suggested Wnt inhibits PM development during somitogenesis, we find that in zebrafish embryos Wnt signaling is sufficient to repress PM development during anterior-posterior patterning. Importantly, the temporal sensitivity of dorso-anterior PMs to increased Wnt signaling largely overlaps with when Wnt signaling promotes specification of the adjacent cardiac progenitors. Furthermore, we find that excess early Wnt signaling can cell autonomously promote expansion of the first heart field (FHF) progenitors at the expense of PM and SHF within the anterior lateral plate mesoderm (ALPM). Our study provides insight into an antagonistic developmental mechanism that balances the sizes of the adjacent cardiac and PM progenitor fields in early vertebrate embryos.

Hey2 regulates the size of the cardiac progenitor pool during vertebrate heart development

“…However, although cardiac cell fate diversification has been elegantly studied via clonal analysis (Meilhac et al, 2003;Lescroart et al, 2010;Devine et al, 2014), how the magnitude of contribution to the developing heart from the CPC pool is regulated remains poorly understood. This process has perhaps been most examined in SHF progenitors, where several signaling pathways have been implicated in regulating the balance of CPC maintenance/proliferation and differentiation (Prall et al, 2007;Ryckebusch et al, 2008;Sirbu et al, 2008;Tirosh-Finkel et al, 2010;Zhao et al, 2014;Li et al, 2016;Mandal et al, 2017). Notable among these are fibroblast growth factor (FGF) and retinoic acid (RA) signaling, the balance of which fine-tunes the specification and differentiation of cardiac progenitors (Ilagan et al, 2006;Park et al, 2008;Rochais et al, 2009;Sorrell and Waxman, 2011;Witzel et al, 2012).…”

A single cell transcriptional roadmap for cardiopharyngeal fate diversification

“…the right ventricle and outflow tract) share a common origin with branchiomeric head muscles, in the cardiopharyngeal mesoderm of the early embryo (Diogo et al, 2015a;Gopalakrishnan et al, 2015;Harel et al, 2012;Lescroart et al, 2010Lescroart et al, , 2014Lescroart et al, , 2015Mandal et al, 2017;Nathan et al, 2008;Tirosh-Finkel et al, 2006;Tzahor and Evans, 2011) .…”

“…The cellular and molecular characteristics of multipotent cardiopharyngeal progenitors, and the mechanisms underlying the early heart vs. pharyngeal/branchiomeric muscle fate choices remain largely elusive, and studies are partially hindered by the complexity of early vertebrate embryos (Chan et al, 2016;Mandal et al, 2017) . Single cell approaches thus offer an opportunity to uncover the molecular underpinnings of early cardiopharyngeal development.…”

Cardiopharyngeal Progenitor Specification: Multiple Roads to the Heart and Head Muscles

“…In fish, tbx1 is also required to specify the nkx2.5+ CPF. Moreover, recent studies have also shown a role for Wnt signaling in the balance between cardiac and skeletal muscle lineages, as Wnt activation during or prior to gastrulation inhibits pharyngeal muscle specification at the expense of cardiac lineages (Mandal et al 2017). Such a role for Wnt has not been found in tunicates (Kaplan et al 2019).…”