The Webb lab studies the pivotal role of cell migration in many important phenomena including embryonic development, cancer, and mental retardation, focusing on signaling pathways regulating adhesion and cytoskeletal dynamics. They also study the signaling pathways that regulate the formation of dendritic spines and synapses in the developing nervous system, using hippocampal neurons from rat embryos.
Dendritic spines are small, actin-rich protrusions that receive most of the excitatory synaptic inputs in the CNS. Spines are believed to mediate the synaptic plasticity that underlies cognitive functions, such as learning and memory. Despite its importance, the molecular mechanisms that regulate the formation of spines and synapses have only begun to be addressed. Work in the Webb lab has led to the hypothesis that local activation of Rac (in the Rho family of small GTPases) is central for synapse and spine formation. Consistent with this work, 3 of 7 recently identified genes mutated in the developmental disorder of nonsyndromic mental retardation are involved in Rho family signaling. The Webb lab utilizes live cell imaging in combination with biochemical and molecular techniques to identify the signaling pathway(s) by which actin regulators modulate spine and synapse formation.