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Biomedical subjects

Craig C Mello

Publications and source records attributed to Craig C Mello.

21 records · Page 2Linked to original sources

The GEX-2 and GEX-3 proteins are required for tissue morphogenesis and cell migrations in C. elegans.

During body morphogenesis precisely coordinated cell movements and cell shape changes organize the newly differentiated cells of an embryo into functional tissues. Here we describe two genes, gex-2 and gex-3, whose activities are necessary for initial steps of body morphogenesis in Caenorhabditis elegans. In the absence of gex-2 and gex-3 activities, cells differentiate properly but fail to become organized. The external hypodermal cells fail to spread over and enclose the embryo and instead cluster on the dorsal side. Postembryonically gex-3 activity is required for egg laying and for proper morphogenesis of the gonad. GEX-2 and GEX-3 proteins colocalize to cell boundaries and appear to directly interact. GEX-2 and GEX-3 are highly conserved, with vertebrate homologs implicated in binding the small GTPase Rac and a GEX-3 Drosophila homolog, HEM2/NAP1/KETTE, that interacts genetically with Rac pathway mutants. Our findings suggest that GEX-2 and GEX-3 may function at cell boundaries to regulate cell migrations and cell shape changes required for proper morphogenesis and development.

Adaptor Proteins, Signal Transducing↗

RNAi (Nematodes: Caenorhabditis elegans).

RNA interference in Caenorhabditis elegans is a type of homology dependent posttranscriptional gene silencing induced by dsRNA. In this chapter we describe the history of the discovery of RNAi, its systemic nature, inheritance, and connection to other homology-dependent silencing phenomena like co-suppression and transcriptional gene silencing. We discuss RNAi-deficient mutants in C. elegans as well as characterized components of the RNAi, pathway, the molecular mechanism of RNAi, and its possible role in development and immunity.

Animals↗

SRC-1 and Wnt signaling act together to specify endoderm and to control cleavage orientation in early C. elegans embryos.

In early C. elegans embryos, signaling between a posterior blastomere, P2, and a ventral blastomere, EMS, specifies endoderm and orients the division axis of the EMS cell. Although Wnt signaling contributes to this polarizing interaction, no mutants identified to date abolish P2/EMS signaling. Here, we show that two tyrosine kinase-related genes, src-1 and mes-1, are required for the accumulation of phosphotyrosine between P2 and EMS. Moreover, src-1 and mes-1 mutants strongly enhance endoderm and EMS spindle rotation defects associated with Wnt pathway mutants. SRC-1 and MES-1 signal bidirectionally to control cell fate and division orientation in both EMS and P2. Our findings suggest that Wnt and Src signaling function in parallel to control developmental outcomes within a single responding cell.

Animals↗