Novel cysteine-rich motif and homeodomain in the product of the Caenorhabditis elegans cell lineage gene lin-11

The gene lin-11 is required for the asymmetric division of a vulval precursor cell type in the nematode Caenorhabditis elegans. Putative lin-11 complementary DNAs were sequenced and found to encode a protein that contains both a homeodomain and two tandem copies of a novel cysteine-rich motif: C-X2-C-X17-19-H-X2-C-X2-C-X2-C-X7-11-(C)-X8-C. Two tandem copies of this motif are also present amino-terminal to the homeodomains in the proteins encoded by the genes mec-3, which is required for C. elegans touch neuron differentiation, and isl-1, which encodes a rat insulin I gene enhancer-binding protein. The arrangement of cysteine residues in this motif, referred to as LIM (for lin-11 isl-1 mec-3), suggests that this region is a metal-binding domain. The presence in these three proteins of both a potential metal-binding domain and a homeodomain distinguishes them from previously characterized proteins.     

Phagocytosis promotes programmed cell death in C. elegans.

In the nematode Caenorhabditis elegans programmed cell death requires the killer genes egl-1, ced-4 and ced-3 (refs 1 and 2), and the engulfment of dying cells requires the genes ced-1, ced-2, ced-5, ced-6, ced-7, ced-10 and ced-12 (refs 3,4,5). Here we show that engulfment promotes programmed cell death. Mutations that cause partial loss of function of killer genes allow the survival of some cells that are programmed to die, and mutations in engulfment genes enhance the frequency of this cell survival. Furthermore, mutations in engulfment genes alone allow the survival and differentiation of some cells that would normally die. Engulfment genes probably act in engulfing cells to promote death, as the expression in engulfing cells of ced-1, which encodes a receptor that recognizes cell corpses, rescues the cell-killing defects of ced-1 mutants. We propose that engulfing cells act to ensure that cells triggered to undergo programmed cell death by the CED-3 caspase die rather than recover after the initial stages of death.     

MicroRNA expression profiles classify human cancers

Recent work has revealed the existence of a class of small non-coding RNA species, known as microRNAs (miRNAs), which have critical functions across various biological processes. Here we use a new, bead-based flow cytometric miRNA expression profiling method to present a systematic expression analysis of 217 mammalian miRNAs from 334 samples, including multiple human cancers. The miRNA profiles are surprisingly informative, reflecting the developmental lineage and differentiation state of the tumours. We observe a general downregulation of miRNAs in tumours compared with normal tissues. Furthermore, we were able to successfully classify poorly differentiated tumours using miRNA expression profiles, whereas messenger RNA profiles were highly inaccurate when applied to the same samples. These findings highlight the potential of miRNA profiling in cancer diagnosis.     

Caenorhabditis elegans early embryogenesis and vulval morphogenesis require chondroitin biosynthesis

Defects in glycosaminoglycan biosynthesis disrupt animal development and can cause human disease. So far much of the focus on glycosaminoglycans has been on heparan sulphate. Mutations in eight squashed vulva (sqv) genes in Caenorhabditis elegans cause defects in cytokinesis during embryogenesis and in vulval morphogenesis during postembryonic development. Seven of the eight sqv genes have been shown to control the biosynthesis of the glycosaminoglycans chondroitin and heparan sulphate. Here we present the molecular identification and characterization of the eighth gene, sqv-5. This gene encodes a bifunctional glycosyltransferase that is probably localized to the Golgi apparatus and is responsible for the biosynthesis of chondroitin but not heparan sulphate. Our findings show that chondroitin is crucial for both cytokinesis and morphogenesis during C. elegans development.     

A genetic pathway for the development of the Caenorhabditis elegans HSN motor neurons

Thirty-five genes define a pathway for the development of the hermaphrodite-specific neurons (HSNs) in Caenorhabditis elegans. Some of these genes affect only one HSN trait, demonstrating that HSN migration, axonal outgrowth and serotonin expression are mutually independent events in HSN development; others, some of which are regulatory, affect multiple HSN traits. Nearly all are pleiotropic, revealing that the genes specifying HSN development also function in the development of other cell types.