ANALYSIS OF A CAENORHABDITIS-ELEGANS TWIST HOMOLOG IDENTIFIES CONSERVED AND DIVERGENT ASPECTS OF MESODERMAL PATTERNING

Mesodermal development is a multistep process in which cells become in creasingly specialized to form specific tissue types. In Drosophila an d mammals, proper segregation and patterning of the mesoderm involves the bHLH factor Twist. We investigated the activity of a Twist-related factor, CeTwist, during Caenorhabditis elegans mesoderm development. Embryonic mesoderm in C. elegans derives from a number of distinct fou nder cells that are specified during the early lineages! in contrast, a single blast cell (M) is responsible for all nongonadal mesoderm for mation during postembryonic development. Using immunofluorescence and reporter fusions, we determined the activity pattern of the gene encod ing CeTwist. No activity was observed during specification of mesoderm al lineages in the early embryo; instead, the gene was active within t he M lineage and in a number of mesodermal cells with nonstriated musc le fates. A role for CeTwist in postembryonic mesodermal cell fate spe cification was indicated by ectopic expression and genetic interferenc e assays. These experiments showed that CeTwist was responsible for ac tivating two target genes normally expressed in specific subsets of no nstriated muscles derived from the M lineage. In vitro and in vivo ass ays suggested that CeTwist cooperates with the C. elegans E/Daughterle ss homolog in directly activating these targets. The two target genes that we have studied, ceh-24 and eg1-15, encode an NK-2 class homeodom ain and an FGF receptor (FGFR) homolog, respectively. Twist activates FGFR and NK-homeodomain target genes during mesodermal patterning of D rosophila and similar target interactions have been proposed to modula te mesenchymal growth during closure of the vertebrate skull. These re sults suggest the possibility that a conserved pathway may be used for diverse functions in mesodermal specification.