title: microRNA-31 modulates skeletal patterning in the sea urchin embryo.
abstract: MicroRNAs (miRNAs) are small non-coding RNAs that repress the translation and reduce the stability of target mRNAs in animal cells. microRNA-31 (miR-31) is known to play a role in cancer, bone formation and lymphatic development. However, studies to understand the function of miR-31 in embryogenesis have been limited. We examined the regulatory role of miR-31 in early development using the sea urchin as a model. miR-31 is expressed at all stages of development and its knockdown (KD) disrupts the patterning and function of primary mesenchyme cells (PMCs), which form the embryonic skeleton spicules. We identified that miR-31 directly represses Pmar1, Alx1, Snail and VegfR7 within the PMC gene regulatory network using reporter constructs. Further, blocking the miR-31-mediated repression of Alx1 and/or VegfR7 in the developing embryo resulted in defects in PMC patterning and skeletogenesis. The majority of the mislocalized PMCs in miR-31 KD embryos did not express VegfR10, indicating that miR-31 regulates VegfR gene expression within PMCs. In addition, miR-31 indirectly suppresses Vegf3 expression in the ectoderm. These results indicate that miR-31 coordinately suppresses genes within the PMCs and in the ectoderm to impact PMC patterning and skeletogenesis. This study identifies the novel function and molecular mechanism of miR-31-mediated regulation in the developing embryo.
authors.affiliation: Department of Biological Sciences, University of Delaware, Newark, DE 19716, USA.
authors.forename: Nadezda A
authors.initials: NA
authors.lastname: Stepicheva
authors.affiliation: Department of Biological Sciences, University of Delaware, Newark, DE 19716, USA jsong@udel.edu.
authors.forename: Jia L
authors.initials: JL
authors.lastname: Song
mesh_terms: D000818:Animals; D004625:Embryo, Nonmammalian / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D053263:Gene Regulatory Networks; D018398:Homeodomain Proteins / Q000378:metabolism; D008648:Mesoderm / Q000166:cytology / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D010012:Osteogenesis; D040262:Receptors, Vascular Endothelial Growth Factor / Q000235:genetics; D012617:Sea Urchins / Q000196:embryology* / Q000235:genetics / Q000378:metabolism
chemical_list: D018398:Homeodomain Proteins; D035683:MicroRNAs; D040262:Receptors, Vascular Endothelial Growth Factor
keywords: Alx1; Cell migration; Cell patterning; Filopodia; MicroRNA; Pmar1; Primary mesenchyme cell; Snail; Strongylocentrotus purpuratus; Vegf signaling; VegfR