Nuclear substructure and dynamics

نویسندگان

  • Angus I Lamond
  • Judith E Sleeman
چکیده

normal cell fate decisions are reiterated in subsequent larval stages. Examples include mutations in lin-4 and lin-29. Worms with such mutations do not express certain adult cell fates, despite being sexually mature (Figure 1). Is there conservation in heterochronic gene pathways? An important regulator of the larval-to-adult transition in worms, let-7, is conserved across diverse phyla, having been identified in flies, sea urchins, humans and many other organisms. In addition, it has recently been demonstrated that the C. elegans heterochronic gene lin-57 is a worm homolog of the Drosophila gene hunchback (hence its new name hbl-1). In the developing central nervous system of flies, hunchback regulates the temporal patterning of cell fate specification for neuroblasts. But doesn't hunchback regulate spatial patterning in flies? Hunchback is indeed best known for its role in anterior–posterior patterning in the early fly embryo; it encodes a zinc-finger transcription factor that acts to establish spatial domains of gene expression. Although downstream effectors are unknown in worms, it is possible that hbl-1 is able to establish analogous temporal domains of gene expression. What's the deal with microRNAs and how are they involved in the heterochronic gene pathway? microRNAs are now appreciated as a new class of small non-coding RNAs. They are likely to act by regulating translation of target mRNAs through binding to sequences in the 3′ untranslated regions with partial anti-sense complementarity. When the product of the lin-4 heterochronic gene was found to be a small, non-coding RNA in 1993, it appeared that it might be a C. elegans-specific, molecular oddity. A second small non-coding RNA, let-7, was discovered in the heterochronic gene pathway in 2000, followed by the cloning of hundreds of small non-coding RNAs (microRNAs) in 2001 and beyond, and it is now appreciated that the heterochronic genes lin-4 and let-7 are the founding members of a larger microRNA gene family. Are microRNAs involved in other pathways? Although the first two microRNAs identified are in the heterochronic gene pathway, there is now evidence for roles of microRNAs in cell proliferation, cell death, fat metabolism and stress resistance in flies. Is there anything we don't know? The mechanism of action of many heterochronic genes remains to be determined. For example, lin-14 encodes a novel nuclear protein with no identified downstream effectors to date. In addition, emerging evidence of phylogenetic conservation of heterochronic genes leads to the prospect that mechanisms to control developmental timing will …

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عنوان ژورنال:
  • Current Biology

دوره 13  شماره 

صفحات  -

تاریخ انتشار 2003