Developmental Genetics; Homeotic and Segmentation Genes; Pattern Formation in
Early Development
A 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.
Search: [ current | former scholar ] [ current | awarded institution ] [ quick search ]
