PMID- 33484703
OWN - NLM
STAT- MEDLINE
DCOM- 20210623
LR  - 20240331
IS  - 1095-564X (Electronic)
IS  - 0012-1606 (Print)
IS  - 0012-1606 (Linking)
VI  - 472
DP  - 2021 Apr
TI  - microRNA-31 regulates skeletogenesis by direct suppression of Eve and Wnt1.
PG  - 98-114
LID - S0012-1606(21)00020-8 [pii]
LID - 10.1016/j.ydbio.2021.01.008 [doi]
AB  - microRNAs (miRNAs) play a critical role in a variety of biological processes, 
      including embryogenesis and the physiological functions of cells. Evolutionarily 
      conserved microRNA-31 (miR-31) has been found to be involved in cancer, bone 
      formation, and lymphatic development. We previously discovered that, in the sea 
      urchin, miR-31 knockdown (KD) embryos have shortened dorsoventral connecting 
      rods, mispatterned skeletogenic primary mesenchyme cells (PMCs) and shifted and 
      expanded Vegf3 expression domain. Vegf3 itself does not contain miR-31 binding 
      sites; however, we identified its upstream regulators Eve and Wnt1 to be directly 
      suppressed by miR-31. Removal of miR-31's suppression of Eve and Wnt1 resulted in 
      skeletal and PMC patterning defects, similar to miR-31 KD phenotypes. 
      Additionally, removal of miR-31's suppression of Eve and Wnt1 results in an 
      expansion and anterior shift in expression of Veg1 ectodermal genes, including 
      Vegf3 in the blastulae. This indicates that miR-31 indirectly regulates Vegf3 
      expression through directly suppressing Eve and Wnt1. Furthermore, removing 
      miR-31 suppression of Eve is sufficient to cause skeletogenic defects, revealing 
      a novel regulatory role of Eve in skeletogenesis and PMC patterning. Overall, 
      this study provides a proposed molecular mechanism of miR-31's regulation of 
      skeletogenesis and PMC patterning through its cross-regulation of a Wnt signaling 
      ligand and a transcription factor of the endodermal and ectodermal gene 
      regulatory network.
CI  - Copyright (c) 2021 Elsevier Inc. All rights reserved.
FAU - Sampilo, Nina Faye
AU  - Sampilo NF
AD  - Department of Biological Sciences, University of Delaware, Newark, DE, 19716, 
      USA.
FAU - Stepicheva, Nadezda A
AU  - Stepicheva NA
AD  - Department of Ophthalmology, University of Pittsburgh School of Medicine, 
      Pittsburgh, PA, 15261, USA.
FAU - Song, Jia L
AU  - Song JL
AD  - Department of Biological Sciences, University of Delaware, Newark, DE, 19716, 
      USA. Electronic address: jsong@udel.edu.
LA  - eng
GR  - P20 GM103446/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20210120
PL  - United States
TA  - Dev Biol
JT  - Developmental biology
JID - 0372762
RN  - 0 (Homeodomain Proteins)
RN  - 0 (MicroRNAs)
RN  - 0 (Transcription Factors)
RN  - 0 (Wnt1 Protein)
SB  - IM
MH  - Animals
MH  - Animals, Genetically Modified
MH  - Body Patterning/genetics
MH  - Embryonic Development/genetics
MH  - Female
MH  - *Gene Expression Regulation, Developmental
MH  - Gene Knockdown Techniques
MH  - Gene Regulatory Networks
MH  - Homeodomain Proteins/*metabolism
MH  - Male
MH  - Mesenchymal Stem Cells/metabolism
MH  - MicroRNAs/genetics/*metabolism
MH  - Musculoskeletal Development/*genetics
MH  - Phenotype
MH  - Signal Transduction/genetics
MH  - Strongylocentrotus purpuratus/*embryology/*genetics/metabolism
MH  - Transcription Factors/metabolism
MH  - Wnt1 Protein/*metabolism
PMC - PMC7956219
MID - NIHMS1668030
OTO - NOTNLM
OT  - Even-skipped
OT  - MicroRNA-31
OT  - Post-transcriptional regulation
OT  - Primary mesenchyme cells
OT  - Sea urchin
OT  - Vegf signaling
OT  - Wnt
OT  - miRNA target protector
EDAT- 2021/01/24 06:00
MHDA- 2021/06/24 06:00
PMCR- 2022/04/01
CRDT- 2021/01/23 20:08
PHST- 2020/08/15 00:00 [received]
PHST- 2020/12/23 00:00 [revised]
PHST- 2021/01/11 00:00 [accepted]
PHST- 2021/01/24 06:00 [pubmed]
PHST- 2021/06/24 06:00 [medline]
PHST- 2021/01/23 20:08 [entrez]
PHST- 2022/04/01 00:00 [pmc-release]
AID - S0012-1606(21)00020-8 [pii]
AID - 10.1016/j.ydbio.2021.01.008 [doi]
PST - ppublish
SO  - Dev Biol. 2021 Apr;472:98-114. doi: 10.1016/j.ydbio.2021.01.008. Epub 2021 Jan 
      20.