B. Ian Hutchins

E-mail: bihutchins@wisc.edu

Research Project:

In the developing brain, neurons make connections with their target cells by sending axons tipped with motile growth cones into the cellular environment. These growth cones guide the axon to appropriate targets by responding to molecular cues. Development of axon branches is an important aspect of axon guidance in the mammalian CNS. Calcium signaling in the growth cone is important for determining rates of axon outgrowth and in responding to guidance cues. In situations where the axon has branched, growth cones at the tips of branches are exposed to different environmental guidance cues and show different rates of outgrowth. My thesis work will be to investigate the role of calcium signaling in axon guidance and branching. Using the developing rodent cortex as a model system, I will carry out live cell fluorescence calcium imaging of dissociated neuron cell culture. This approach permits precise imaging of calcium dynamics in living cells. Direct local application of guidance factors and photorelease of caged signaling molecules at spatially separated growth cones in vitro will enable precise examination of their effects on growth cone calcium dynamics in the primary axon and its branches. The use of cortical slice preparation and two-photon fluorescence microscopy will extend this work to an in vivo model of the role of calcium signaling in branching of the developing mammalian cortex. I will also investigate the roles of signaling molecules downstream of calcium to determine their role in regulating the behavior of spatially separated growth cones of the same axon.

Abstracts and Publications:

• Hutchins, B.I., L. Li, and K. Kalil. 2008. Wnt5a regulates cortical axon outgrowth and guidance through calcium signaling mechanisms. Nat. Grad. Stud. Res. Fest. Abstr.
• Li, L., B.I. Hutchins, and K. Kalil. 2008. Wnt5a induces simultaneous cortical axon outgrowth and repulsive axon guidance through distinct signaling mechanisms. Soc. Neurosci. Abstr.
• Hutchins, B.I. and K. Kalil. 2008. Differential outgrowth of axons and their branches is regulated by localized calcium transients. J. Neurosci. 28(1):143-153. [PDF]
• Hutchins, B.I. and K. Kalil. 2007. Regulation of axon outgrowth in the corpus callosum by calcium activity. Soc. Neurosci. Abstr.
• Hutchins, B.I. and K. Kalil. 2006. Localized calcium signaling regulates differential outgrowth of cortical axons and their branches. Soc. Neurosci. Abstr.
• Hutchins, B.I. and K. Kalil. 2006. Localized calcium signaling regulates differential outgrowth of cortical axons and their collateral branches. Axon Guidance, Neural Plasticity and Synaptogenesis CSHL.
• Hutchins, B.I. and K. Kalil. 2005. Netrin-1 can evoke differential calcium activity in restricted regions of axons and their branches. Soc. Neurosci. Abstr.