Interdigital tissue remodelling in the embryonic limb involves dynamic regulation of the mi RNA profiles

Abstract Next‐generation sequencing in combination with quantitative polymerase chain reaction analysis revealed a dynamic mi RNA signature in the interdigital mesoderm of the chick embryonic hinlimb in the course of interdigit remodelling. During this period, 612 previously known chicken mi RNA s (gga‐mi RNA s) and 401 non‐identified sequences were expressed in the interdigital mesoderm. Thirty‐six micro RNA s, represented by more than 750 reads per million, displayed differential expression between stages HH 29 (6 id) and HH 32 (7.5 id), which correspond to the onset and the peak of interdigital cell death. Twenty mi RNA s were upregulated by at least 1.5‐fold, and sixteen were downregulated by at least 0.5‐fold. Upregulated mi RNA s included mi RNA s with recognized proapoptotic functions in other systems (miR‐181 family, miR‐451 and miR‐148a), mi RNA s associated with inflammation and cell senescence (miR‐21 and miR‐146) and mi RNA s able to induce changes in the extracellular matrix (miR‐30c). In contrast, mi RNA s with known antiapoptotic effects in other systems, such as miR‐222 and miR‐205, became downregulated. In addition, miR‐92, an important positive regulator of cell proliferation, was also downregulated. Together, these findings indicate a role for mi RNA s in the control of tissue regression and cell death in a characteristic morphogenetic embryonic process based on massive apoptosis.