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. Author manuscript; available in PMC: 2012 Aug 1.
Published in final edited form as: Curr Opin Genet Dev. 2011 Apr 29;21(4):511–517. doi: 10.1016/j.gde.2011.04.003

Figure 1. MicroRNAs and developmental timing in C. elegans.

Figure 1

MicroRNAs (shaded text boxes) of the lin-4 and let-7-Family control the temporal progression of cell fates in the lateral hypodermal “seam” cell lineages of developing C. elegans larvae. In each of stages L1-L4, seam cells undergo a single round of stem cell-like self-renewal divisions (wedge-shaped bars), with a single symmetric division (red bar) interposed in the L2 stage. At the L4 molt, seam cells exit the cell cycle and terminally differentiate (triple bars). MicroRNAs post-transcriptionally regulate key target mRNAs by direct interactions (blue lines) with to 3′ UTR sequences. Down regulation of the transcription factor LIN-14 by lin-4 microRNA is required for progression from the asymmetric L1 division pattern to symmetric division in the L2. Progression from the L2 to the L3 fate is caused by the down regulation of the transcription factor HBL-1 through the redundant activity of microRNAs of the let-7 family, which includes let-7, mir-48, mir-84, and mir-241 [15]. let-7-Family microRNA activity is modulated positively by the TRIM/NHL protein NHL-2 [24]. The L2 to L3 transition also involves down regulation of the RNA binding protein LIN-28 by lin-4 microRNA; LIN-28 acts upstream of the let-7-Family microRNAs [15]. The nuclear hormone receptor is the hub of a complex set of interactions that integrate microRNA and steroid hormone inputs to coordinate temporal cell fates with a decision to enter an optional diapause after the L2 stage [14]. Progression from a cycling status to terminally-differentiation at the L4 molt is conferred by a dramatic up-regulation of let-7 in the L4, resulting in down-regulation of the TRIM/NHL protein LIN-41, and consequent up regulation of the transcription factor LIN-29. HBL-1 represses let-7 transcription, ensuring that the up regulation of let-7 microRNA occurs only after completion of earlier steps. The cessation of molting after the L4 stage involves in part the down regulation, by let-7 family microRNAs, of the nuclear hormone receptor molting factors NHR-23 and NHR25 [17].