The microRNA miR-196 acts upstream of Hoxb8 and Shh in limb development.

Publication Type:

Journal Article


Nature, Volume 438, Issue 7068, p.671-4 (2005)


Animals, Base Sequence, Chick Embryo, Down-Regulation, Extremities, Gene Expression Regulation, Developmental, Hedgehog Proteins, Homeodomain Proteins, Mice, MicroRNAs, Organ Specificity, Ribonuclease III, Trans-Activators, Transcription, Genetic, Tretinoin


<p>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.</p>