Figure 2. Evolutionary conservation of developmental timing roles for microRNAs.

A. In nematodes, insects and mammals, let-7 family microRNAs control progression from earlier, or more proliferative states, to later, more differentiated states. These conserved activities in developmental progression can involve explicitly conserved targets (red), and non-conserved targets (blue). C. elegans let-7 family microRNAs act in several cell types to control early-to-late cell fate progression. Examples of targets that are conserved between C. elegans and mammals and insects include LIN-28, LET-60/Ras and LIN-41. Nonconserved targets of let-7 can nevertheless mediate roles for let-7 in promoting transitions from more primitive to more differentiated developmental states: examples include in Drosophila the down regulation of Abrupt in the control of a reorganization of the neuromusculature at metamorphosis [45],[46], and in humans the down regulation of the oncogene HMGA2 [67]. B. MicroRNAs of families other than let-7 can also control temporal developmental transitions, such as the case of miR-96, which is required for a program of differentiation in mammalian inner ear hair cells [53]. There could be multiple relevant targets of miR-96 in this context, since many mRNAs are deregulated in mir-96 mutant mice [51].