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First published online October 13, 2005
doi: 10.1242/10.1242/dev.02073

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MicroRNA functions in animal development and human disease

The Wellcome Trust/Cancer Research UK Gurdon Institute and Department of Biochemistry, The Henry Wellcome Building of Cancer and Developmental Biology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK

View larger version (32K): [in a new window]   Fig. 1. MicroRNAs control developmental timing. (A) C. elegans cell lineage diagram for the seam cells V1-V4 and V6. Developmental time is the vertical axis. 1 to 4, larval stages L1 to L4; A, adult stages. Colours refer to developmental stage. H, cell fused to hypodermis. Triple black line, terminal differentiation signified by lateral alae. Dotted lines, continued cell division according to the same pattern. (B) Simplified genetic pathway of the heterochronic genes in C. elegans. Dashed line represents possible late role for mir-48, mir-84 and mir-241 during development.

View larger version (18K): [in a new window]   Fig. 2. MicroRNAs control differentiation. Neuronal specification of ASEL and ASER cells by lsy-6 microRNA and miR-273. che-1, unc-37 and ceh-36/lin-49 are required for the neuronal determination of the pair of ASE neurons. The ASE cells differ in the asymmetric expression of two candidate chemoreceptor genes, gcy-7 (in ASEL) and gcy-5 (in ASER), which also define different chemosensory functions. The microRNA lsy-6 represses the translation of cog-1 mRNA, which results in the expression of lim-6 and gcy-7 (shown in green). In ASER, miR-273 represses the translation of die-1 mRNA, which leads to the expression of cog-1 and gcy-5 (shown in red). It is still unclear where che-1 acts in this pathway.

View larger version (13K): [in a new window]   Fig. 3. MicroRNAs control programmed cell death. The D. melanogaster microRNA bantam and miR-14 inhibit programmed cell death. (A) The mRNA of the pro-apoptotic gene hid (yellow) has five predicted target sites for the bantam microRNA (blue) in the 3'UTR. (B) The alignment of the bantam microRNA with one of these sites is shown in green. (C) miR-14 also inhibits programmed cell death, possibly by regulating several pro-apoptotic genes such as reaper, hid/wrinkled, grim and Dronc.

View larger version (18K): [in a new window]   Fig. 4. MicroRNA family conservation. MicroRNAs can be grouped into families according to primary sequence similarity. As a cut-off, we used less than five conserved nucleotides out of the first eight. This Venn diagram shows the conservation of microRNA families between C. elegans, D. melanogaster and mammals. Primary sequence data was obtained from MiRBase version 7.0 (Griffiths-Jones, 2004).