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Background  The  Hox  genes are involved in patterning the anterior-posterior axis. In addition to the protein coding  Hox  genes, the  miR-10 ,  miR-196  and  miR-615  families of microRNA genes are conserved within the vertebrate  Hox  clusters. The members of the  miR-10  family are located at positions associated with  Hox-4  paralogues. No function is yet known for this microRNA family but the genomic positions of its members suggest a role in anterior-posterior patterning.    Methodology/Principal Findings  Using sensor constructs, overexpression and morpholino knockdown, we show in Zebrafish that  miR-10  targets  HoxB1a  and  HoxB3a  and synergizes with  HoxB4  in the repression of these target genes. Overexpression of  miR-10  also induces specific phenotypes related to the loss of function of these targets.  HoxB1a  and  HoxB3a  have a dominant hindbrain expression domain anterior to that of  miR-10  but overlap in a weaker expression domain in the spinal cord. In this latter domain,  miR-10  knockdown results in upregulation of the target genes. In the case of a  HoxB3a  splice variant that includes  miR-10c  within its primary transcript, we show that the microRNA acts in an autoregulatory fashion.    Conclusions/Significance  We find that  miR-10  acts to repress  HoxB1a  and  HoxB3a  within the spinal cord and show that this repression works cooperatively with  HoxB4 . As with the previously described interactions between  miR-196  and  HoxA7  and  Hox-8  paralogues, the target genes are located in close proximity to the microRNA. We present a model in which we postulate a link between the clustering of  Hox  genes and post-transcriptional gene regulation. We speculate that the high density of transcription units and enhancers within the  Hox  clusters places constraints on the precision of the transcriptional control that can be achieved within these clusters and requires the involvement of post-transcriptional gene silencing to define functional domains of genes appropriately.

MiR-10 Represses HoxB1a and HoxB3a in Zebrafish