Our long-term goal is to unravel the molecular mechanism(s) driving mammalian neural development, first by identifying key players, and then determining their functions and the molecular pathways involved. To identify the genes that guide development of the mouse nervous system, we use a direct genetic approach and screen for recessive mutations that disrupt embryonic neural development. This enables the mouse embryo to “tell” us, in an unbiased manner, which genes are critical to form a nervous system. While this approach is undoubtedly laborious, it offers two advantages. First, it is in vivo, making the results physiologically relevant. Second, it teaches us what is critical in mammals. For example, a mouse mutant identified via forward genetics first revealed that cilia are required for vertebrate Hedgehog (Hh) signaling, despite years of work in fruit flies. The link between cilia and Hh signaling inspired a series of discoveries that transformed the cilium to a fundamental cellular signaling organelle. This finding, however, brought a new challenge to the field. Most mouse mutants ablated cilia and signaling altogether, creating a technical conundrum, a “chicken-or-egg”-type mystery. Our most impactful work stems from the mutants we study that resolve this conundrum. For example, much of our work focuses on the regulatory GTPase, Arl13b, which perturbs but does not ablate ciliogenesis, allowing us to uncouple ciliary signaling from ciliogenesis itself.
For more detailed information, please see the Current Projects page.