Our long term goal is to understand the molecular mechanisms through which different classes of regulatory genes work together to control development. A fundamental problem in developmental biology is to understand how embryonic cells sense their positions in the embryo and then participate in forming tissues and structures that are appropriate to those positions. This proposal is focused upon genes that appear to be involved in this """"""""positional information"""""""" process. In the fruit fly Drosophila extensive gentic screens have led to the identification of many of the genes that control the earliest embryonic pattern formation events such as genes that control the dividion of the embryo into segments or the differentiation of the segments into distinctive structures. Among the segmentation genes is one, patched (ptc), that is likely to be involved in the generation or interpretation of positional information. Mutations in ptc cause embryos to develop with part of the pattern missing from each segment. In each segment, in place of the missing pattern elements is a mirror-image duplication of some of the remaining pattern elements, including the segment boundaries so the mutant embryos have twice the usual number of segment boundaries. No other segmentation gene has a phenotype like that of ptc, although a group of other genes has in common a phenotype involving mirror-image duplications. The ptc phenotype results from incorrect determination of cell fates, and not from death of cells followed by regeneration. Thus cells fail to properly sense their postions, or fail to act appropriately according to their postions. To begin a study of the molecular basis of this phenomenon, DNA clones containing a gene that is likely to be patched have been isolated. We propose a multifaceted study of patched function, including continued developmental analysis, characterization of its interactions with other segmentation genes, investigation of its gene structure, and studies of its protein product(s).
| Hooper, J E; Scott, M P (1989) The Drosophila patched gene encodes a putative membrane protein required for segmental patterning. Cell 59:751-65 |
