Matthew P. Scott
Board Member: 2003 - 2005
Developmental Genetics; Homeotic and Segmentation Genes; Pattern Formation in Early DevelopmentA fundamental problem in developmental biology is how genes orchestrate differentiation and multicellular organization. Homeotic mutations cause part of an animal to develop as a copy of another part, transforming mouse vertebrae into more anterior or posterior forms, chicken wing or leg digits into a duplicate of other digits, and fly (Drosophila) antennae into legs. A remarkable cluster of homeotic genes exists in all animals and encodes a set of transcription factors which have in common a DNA binding domain called the homeodomain, a protein structure at least a billion years old. Each homeotic transcription factor acts in a different region along the anterior-posterior axis of the animal, in muscle, nerve, and epidermis, to govern what structures form. How do different homeotic proteins drive formation of different structures? We are investigating how each gene is expressed in its proper domain--the upstream problem, what genes are regulated by the homeotic transcription factors--the downstream problem, and what cofactors work with homeotic proteins to control tissue-specific regulatory events. Several of the interacting genes, upstream and downstream, are related to vertebrate proto-oncogenes.
A second area of the laboratory's interest also involves pattern formation, but focuses on cell-cell communication events which inform the cells of both their appropriate fates and their polarity within developing structures. The "segment polarity" genes, which affect both types of information, encode signal transduction components as well as transcription factors. One segment polarity gene, patched, encodes a novel trans-membrane protein which controls cell fates and polarities. We are studying patched and two other newly isolated genes which interact with it.