PMID- 26400092 OWN - NLM STAT- MEDLINE DCOM- 20160307 LR - 20190108 IS - 1477-9129 (Electronic) IS - 0950-1991 (Print) IS - 0950-1991 (Linking) VI - 142 IP - 21 DP - 2015 Nov 1 TI - microRNA-31 modulates skeletal patterning in the sea urchin embryo. PG - 3769-80 LID - 10.1242/dev.127969 [doi] AB - 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. CI - (c) 2015. Published by The Company of Biologists Ltd. FAU - Stepicheva, Nadezda A AU - Stepicheva NA AD - Department of Biological Sciences, University of Delaware, Newark, DE 19716, USA. FAU - Song, Jia L AU - Song JL AD - Department of Biological Sciences, University of Delaware, Newark, DE 19716, USA jsong@udel.edu. LA - eng GR - P20 GM103446/GM/NIGMS NIH HHS/United States GR - P20 GM103653/GM/NIGMS NIH HHS/United States GR - 1P20GM10365301A/GM/NIGMS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20150923 PL - England TA - Development JT - Development (Cambridge, England) JID - 8701744 RN - 0 (Homeodomain Proteins) RN - 0 (MicroRNAs) RN - EC 2.7.10.1 (Receptors, Vascular Endothelial Growth Factor) SB - IM MH - Animals MH - Embryo, Nonmammalian/metabolism MH - Gene Expression Regulation, Developmental MH - Gene Regulatory Networks MH - Homeodomain Proteins/metabolism MH - Mesoderm/cytology/metabolism MH - MicroRNAs/genetics/*metabolism MH - Osteogenesis MH - Receptors, Vascular Endothelial Growth Factor/genetics MH - Sea Urchins/*embryology/genetics/metabolism PMC - PMC4647217 OTO - NOTNLM OT - Alx1 OT - Cell migration OT - Cell patterning OT - Filopodia OT - MicroRNA OT - Pmar1 OT - Primary mesenchyme cell OT - Snail OT - Strongylocentrotus purpuratus OT - Vegf signaling OT - VegfR COIS- Competing interests The authors declare no competing or financial interests. EDAT- 2015/09/25 06:00 MHDA- 2016/03/08 06:00 PMCR- 2016/11/01 CRDT- 2015/09/25 06:00 PHST- 2015/06/29 00:00 [received] PHST- 2015/09/03 00:00 [accepted] PHST- 2015/09/25 06:00 [entrez] PHST- 2015/09/25 06:00 [pubmed] PHST- 2016/03/08 06:00 [medline] PHST- 2016/11/01 00:00 [pmc-release] AID - dev.127969 [pii] AID - DEV127969 [pii] AID - 10.1242/dev.127969 [doi] PST - ppublish SO - Development. 2015 Nov 1;142(21):3769-80. doi: 10.1242/dev.127969. Epub 2015 Sep 23.