We use a genetic approach to identify new genes that control important events in early mouse embryogenesis. We screen for recessive, ENU- induced mutations that cause clear morphological abnormalities at midgestation. Using the completed mouse genome sequence, it is now straightforward to identify the genes responsible for the mutant phenotypes.

This project is a component of the Sloan-Kettering Mouse Project: a collaborative project to screen for mutants that affect 3 stages of mouse embryogenesis. The project has identified more than 100 mutations with clear effects on mouse embryonic. Studies in our lab focus on two classes of mutations: genes that control cell type specification in the nervous system and genes that control specification and morphogenesis of the body axis. In these studies, we have found that there are close connections between embryonic development and cell biology.

Mutations that affect embryonic morphogenesis and patterning act at the level of cell biology. Mesodermal cells from Nap1^khlo embryos lack normal lamellipodia (left); many of the Nap1^khlo embryos have duplications of the anterior-posterior body axis. The organization of the microtubule axoneme of cilia is abnormal in Arl13b^hnn embryos (right); Hedgehog signaling and neural patterning are also abnormal in these embryos.