title: TGF-β sensu stricto signaling regulates skeletal morphogenesis in the sea urchin embryo.
abstract: Cell-cell signaling plays a prominent role in the formation of the embryonic skeleton of sea urchins, but the mechanisms are poorly understood. In the present study, we uncover an essential role for TGF-β sensu stricto signaling in this process. We show that TgfbrtII, a type II receptor dedicated to signaling through TGF-β sensu stricto, is expressed selectively in skeletogenic primary mesenchyme cells (PMCs) during skeleton formation. Morpholino (MO) knockdowns and studies with a specific TgfbrtII inhibitor (ITD-1) in both S. purpuratus and Lytechinus variegatus embryos show that this receptor is required for biomineral deposition. We provide pharmacological evidence that Alk4/5/7 is the cognate TGF-β type I receptor that pairs with TgfbrtII and show by inhibitor treatments of isolated micromeres cultured in vitro that both Alk4/5/7 and TgfbrtII function cell-autonomously in PMCs. Gene expression and gene knockdown studies suggest that TGF-β sensu stricto may be the ligand that interacts with TgfbrtII and support the view that this TGF-β superfamily ligand provides an essential, permissive cue for skeletogenesis, although it is unlikely to provide spatial patterning information. Taken together, our findings reveal that this model morphogenetic process involves an even more diverse suite of cell signaling pathways than previously appreciated and show that PMCs integrate a complex set of both generalized and spatially localized cues in assembling the endoskeleton.
authors.affiliation: Department of Biological Sciences, Carnegie Mellon University, 4400 Fifth Avenue, Pittsburgh, PA 15213, United States.
authors.forename: Zhongling
authors.initials: Z
authors.lastname: Sun
authors.affiliation: Department of Biological Sciences, Carnegie Mellon University, 4400 Fifth Avenue, Pittsburgh, PA 15213, United States. Electronic address: ettensohn@cmu.edu.
authors.forename: Charles A
authors.initials: CA
authors.lastname: Ettensohn
mesh_terms: D030201:Activin Receptors, Type I / Q000378:metabolism; D000818:Animals; D001846:Bone Development / Q000235:genetics; D019070:Cell Lineage; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000378:metabolism*; D054262:Gastrulation / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D017403:In Situ Hybridization; D008024:Ligands; D008648:Mesoderm / Q000166:cytology; D009024:Morphogenesis; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D012617:Sea Urchins / Q000166:cytology / Q000196:embryology* / Q000235:genetics; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: D008024:Ligands; D012333:RNA, Messenger; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D030201:Activin Receptors, Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II
keywords: Biomineralization; Morphogenesis; Primary mesenchyme cells; Sea urchin embryo; Skeleton; TGF-β signaling