My laboratory is interested in the mechanisms which establish and pattern the body axes and organ precursors of the mammalian embryo. We are using the unique genetic technologies available in the mouse to study induction, pattern formation, and morphogenesis, particularly of the central nervous system (CNS). One approach underway is the targeted mutation or mis-expression of candidate genes likely to control these events. Many of these genes function analogously in the development of other organisms, allowing us to exploit the experimental strengths of alternative model systems to devise better mouse experiments.
We also use existing mutant and transgenic mice to probe the roles of cellular and molecular interactions in tissue development. Our studies bear on normal mammalian embryogenesis and on its anomalies, such as human birth defects of the neural tube and skeleton. Projects underway focus primarily on the role of the mammalian Spemann's organizer and its descendents in development of the CNS and axial skeleton. Spemann's organizer is a small group of cells which is believed to be the source of the signals which induce and pattern the neurectoderm, from which the CNS develops. However, analysis of embryos from our gene "knock-out" experiments has shown that neither the organizer nor its known signaling proteins is required for neural induction. Nevertheless, the organizer and its signaling proteins do have essential roles in development of many organs, particularly the neural tube and axial skeleton.
Graduate students in the lab are pursuing several complementary genetic strategies to reveal the molecular and cellular bases for the functions of the organizer, and to unmask alternative mechanisms for neural induction and patterning.
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