title: Gene regulatory network interactions in sea urchin endomesoderm induction.
abstract: A major goal of contemporary studies of embryonic development is to understand large sets of regulatory changes that accompany the phenomenon of embryonic induction. The highly resolved sea urchin pregastrular endomesoderm-gene regulatory network (EM-GRN) provides a unique framework to study the global regulatory interactions underlying endomesoderm induction. Vegetal micromeres of the sea urchin embryo constitute a classic endomesoderm signaling center, whose potential to induce archenteron formation from presumptive ectoderm was demonstrated almost a century ago. In this work, we ectopically activate the primary mesenchyme cell-GRN (PMC-GRN) that operates in micromere progeny by misexpressing the micromere determinant Pmar1 and identify the responding EM-GRN that is induced in animal blastomeres. Using localized loss-of -function analyses in conjunction with expression of endo16, the molecular definition of micromere-dependent endomesoderm specification, we show that the TGFbeta cytokine, ActivinB, is an essential component of this induction in blastomeres that emit this signal, as well as in cells that respond to it. We report that normal pregastrular endomesoderm specification requires activation of the Pmar1-inducible subset of the EM-GRN by the same cytokine, strongly suggesting that early micromere-mediated endomesoderm specification, which regulates timely gastrulation in the sea urchin embryo, is also ActivinB dependent. This study unexpectedly uncovers the existence of an additional uncharacterized micromere signal to endomesoderm progenitors, significantly revising existing models. In one of the first network-level characterizations of an intercellular inductive phenomenon, we describe an important in vivo model of the requirement of ActivinB signaling in the earliest steps of embryonic endomesoderm progenitor specification.
authors.affiliation: National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Aditya J
authors.initials: AJ
authors.lastname: Sethi
authors.forename: Robert C
authors.initials: RC
authors.lastname: Angerer
authors.forename: Lynne M
authors.initials: LM
authors.lastname: Angerer
mesh_terms: D028341:Activins / Q000235:genetics*; D000818:Animals; D001757:Blastomeres / Q000166:cytology; D015815:Cell Adhesion Molecules / Q000235:genetics; D047108:Embryonic Development / Q000235:genetics; D004627:Embryonic Induction / Q000235:genetics*; D005775:Gastrula / Q000166:cytology / Q000254:growth & development; D018507:Gene Expression Regulation, Developmental; D053263:Gene Regulatory Networks; D008648:Mesoderm / Q000166:cytology / Q000196:embryology*; D012617:Sea Urchins / Q000196:embryology / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000235:genetics
chemical_list: D015815:Cell Adhesion Molecules; D016212:Transforming Growth Factor beta; C044147:activin B; C061515:endo16 protein, sea urchin; D028341:Activins