01-P005 In ovo application of antagomiRs indicate a role for miR196 in patterning the chick axial skeleton through Hox gene regulation

revealed a marked reduction in radial thickness starting at E13.5, and defective postnatal cortical layering. Whereas the former was due to neuronal apoptosis starting at E12.5, which was the earliest detectable phenotype, the latter reflected dramatic impairment of neuronal differentiation. Remarkably, the primary target cells of Dicer ablation, the neuroepithelial cells, and the neurogenic progenitors derived from them, were unaffected by miRNA depletion with regard to cell cycle progression, cell division, differentiation and viability during the early stage of neurogenesis, and only underwent apoptosis starting at E14.5. Our results support the emerging concept that progenitors are less dependent on miRNAs than their differentiated progeny. In order to identify miRNAs targets, we extracted total RNA from E13.5 cortices of Dicer-ablated and of control littermates, and mRNAs were subjected to microarray analysis. Our results show that upon miRNA depletion the number of upregulated mRNAs is higher than that of downregulated ones, suggesting that identified mRNAs might represent primary miRNAs targets rather than mRNAs indirectly affected by miRNAs depletion.