Molecular evolution of developmental regulatory pathways

点击翻译按钮获取中文摘要

During development of animals, many cells and cell types (including stem cells) make choices as to when and where to change their 'fate'.  These decisions are controlled by pathways of molecules that act both on the cell (outside or extrinsic factors) and inside the cell (intrinsic).  These 'signal transduction' pathways are critically important for understanding these cellular choices.  Fortunately, the molecules in these pathways are often very similar in even primitive animals, allowing us to use simple animal 'models' for these studies.  In this proposal, we want to do experiments that will allow us to understand what allows these molecular pathways to change and evolve, so that different animals have different characteristics from one another.  We will be using a simple animal, the soil nematode Caenorhabditis, examining the molecules that control a simple choice, that between male and female fates.  We have already shown that in two related Caenorhabditis species (elegans and briggsae), that the same molecules act in different ways to control this choice.  In one species, we have identified many of the relevant factors, while in the second, we have not.  The animal model that we have chosen allows us to use many different approaches (genetics, molecular biology, genomics and cell biology).   The proposed analysis will i) use forward and reverse genetics to assess the respective roles of the sex determining proteins; ii) Use genetics to identify and characterize novel sex- determination loci (particularly those controlling the sperm/oocyte switch); iii) test the C. elegans homologues of these novel genes for any previously unrecognized role in sex determination; and iv) combine the results from these analyses in the two species (plus previous data from other species) to begin a structure-function analysis of the factors.  The results of this analysis will help to address two important questions in developmental biology.  First, (and most specifically) how does the C. elegans sex determination regulatory hierarchy work at the molecular level?  Second (and generally) how do developmental regulatory pathways evolve?