A Genetic Approach to Identifying Signal Transduction Mechanisms Initiated by Receptors for TGF-B-Related Factors.
Annual rept. 1Oct 96-30 Sep 97
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A genetic screen for new mutations affecting the signaling pathway by which cells respond to TGF-beta-related factors was carried out in Drosophila. The genetic background was sensitized using a mutation in the Type I receptor. New mutations affecting the phenotypes caused by the sensitized genetic background were. recovered. The new mutations were mapped to six different genes. Three of these genes were previously known to participate in the signaling pathway, confirming the ability of the screen to recover mutations in the pathway. DNA sequencing was used to establish the molecular lesion in 5 of the new mutations in the Mad gene and in the. type II receptor gene. Positional cloning was. used to identify the gene affected by three mutations recovered in the screen. The gene encodes a TGF-beta-related ligand called 6OA. Phenotypic analysis confirmed the role of this TGF- beta-related ligand in several developmental processes in Drosophila. Recovery in the screen and the phenotypic analysis reveal that 6OA may function as par of a heterodimeric ligand with the Drosophila decapentaplegic protein.
- Medicine and Medical Research