title: S1pr2/Gα13 signaling regulates the migration of endocardial precursors by controlling endoderm convergence.
abstract: Formation of the heart tube requires synchronized migration of endocardial and myocardial precursors. Our previous studies indicated that in S1pr2/Gα13-deficient embryos, impaired endoderm convergence disrupted the medial migration of myocardial precursors, resulting in the formation of two myocardial populations. Here we show that endoderm convergence also regulates endocardial migration. In embryos defective for S1pr2/Gα13 signaling, endocardial precursors failed to migrate towards the midline, and the presumptive endocardium surrounded the bilaterally-located myocardial cells rather than being encompassed by them. In vivo imaging of control embryos revealed that, like their myocardial counterparts, endocardial precursors migrated with the converging endoderm, though from a more anterior point, then moved from the dorsal to the ventral side of the endoderm (subduction), and finally migrated posteriorly towards myocardial precursors, ultimately forming the inner layer of the heart tube. In embryos defective for endoderm convergence due to an S1pr2/Gα13 deficiency, both the medial migration and the subduction of endocardial precursors were impaired, and their posterior migration towards the myocardial precursors was premature. This placed them medial to the myocardial populations, physically blocking the medial migration of the myocardial precursors. Furthermore, contact between the endocardial and myocardial precursor populations disrupted the epithelial architecture of the myocardial precursors, and thus their medial migration; in embryos depleted of endocardial cells, the myocardial migration defect was partially rescued. Our data indicate that endoderm convergence regulates the medial migration of endocardial precursors, and that premature association of the endocardial and myocardial populations contributes to myocardial migration defects observed in S1pr2/Gα13-deficient embryos. The demonstration that endoderm convergence regulates the synchronized migration of endocardial and myocardial precursors reveals a new role of the endoderm in heart development.
authors.affiliation: Department of Anatomy and Cell Biology, Carver College of Medicine, University of Iowa, 1-400 Bowen Science Building, 51 N Road, Iowa City, IA 52242-1109, USA.
authors.forename: Huaping
authors.initials: H
authors.lastname: Xie
authors.affiliation: Department of Anatomy and Cell Biology, Carver College of Medicine, University of Iowa, 1-400 Bowen Science Building, 51 N Road, Iowa City, IA 52242-1109, USA; State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China.
authors.forename: Ding
authors.initials: D
authors.lastname: Ye
authors.affiliation: Department of Developmental Biology, Washington University School of Medicine, St Louis, MO 63110, USA.
authors.forename: Diane
authors.initials: D
authors.lastname: Sepich
authors.affiliation: Department of Anatomy and Cell Biology, Carver College of Medicine, University of Iowa, 1-400 Bowen Science Building, 51 N Road, Iowa City, IA 52242-1109, USA. Electronic address: fang-lin@uiowa.edu.
authors.forename: Fang
authors.initials: F
authors.lastname: Lin
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000235:genetics / Q000502:physiology*; D002465:Cell Movement; D004625:Embryo, Nonmammalian / Q000002:abnormalities / Q000187:drug effects; D004699:Endocardium / Q000196:embryology*; D004707:Endoderm / Q000196:embryology*; D044365:GTP-Binding Protein alpha Subunits, G12-G13 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008164:Luminescent Proteins / Q000032:analysis; D060172:Morpholinos / Q000235:genetics / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics; D029961:Zebrafish Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
chemical_list: D008164:Luminescent Proteins; D060172:Morpholinos; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D029961:Zebrafish Proteins; D044365:GTP-Binding Protein alpha Subunits, G12-G13; C000621729:S1pr2 protein, zebrafish
keywords: Endocardial migration; Endoderm; Gα(13); Imaging; S1pr2/Mil