The microRNA miR-196 acts upstream of Hoxb8 and Shh in limb development.
MicroRNAs (miRNAs) are an abundant class of gene regulatory molecules (reviewed in refs 1, 2). Although computational work indicates that miRNAs repress more than a third of human genes, their roles in vertebrate development are only now beginning to be determined. Here we show that miR-196 acts upstream of Hoxb8 and Sonic hedgehog (Shh) in vivo in the context of limb development, thereby identifying a previously observed but uncharacterized inhibitory activity that operates specifically in the hindlimb. Our data indicate that miR-196 functions in a fail-safe mechanism to assure the fidelity of expression domains that are primarily regulated at the transcriptional level, supporting the idea that many vertebrate miRNAs may function as a secondary level of gene regulation.
Hornstein
Eran
E
Department of Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA.
Mansfield
Jennifer H
JH
Yekta
Soraya
S
Hu
Jimmy Kuang-Hsien
JK
Harfe
Brian D
BD
McManus
Michael T
MT
Baskerville
Scott
S
Bartel
David P
DP
Tabin
Clifford J
CJ
D000818:Animals; D001483:Base Sequence; D002642:Chick Embryo; D015536:Down-Regulation / Q000187:drug effects; D005121:Extremities / Q000196:embryology*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000235:genetics*; D053823:Hedgehog Proteins; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009928:Organ Specificity; D043244:Ribonuclease III / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects / Q000235:genetics; D014212:Tretinoin / Q000494:pharmacology
D053823:Hedgehog Proteins; D018398:Homeodomain Proteins; C095822:Hoxb8 protein, mouse; D035683:MicroRNAs; C465570:Shh protein, mouse; D015534:Trans-Activators; D014212:Tretinoin; D043244:Ribonuclease III