Identification of a molecular system that regulates growth cone membrane potential during growth cone guidance
© Yamada et al; licensee BioMed Central Ltd. 2011
Published: 18 July 2011
Growth cones, at the tips of growing neurites (axons and dendrites) of developing neurons are guided to their synaptic targets by various external guidance molecules to make functional neuronal connections. The mechanisms by which growth cones respond to these external guidance molecules are yet to be elucidated. In cultured Xenopus spinal commissural interneurons (CINs) derived from stage 26-28 embryos, the magnitude of cyclic-GMP (cGMP) signaling determines the direction of growth cone turning in response to a secreted guidance molecule, semaphorin 3A (Sema3A) by controlling growth cone membrane potential shifts . The molecular mechanism of intracellular signaling that controls the growth cone membrane potential is largely unknown. In this study, we aim to identify the molecular interaction between the signaling cascade(s) that regulate(s) the activities of Na+ channels (NaC) and Cl– channels (ClC) by employing Bayesian statistics with parametric models for the computational analysis of experimentally derived data.
We reconstructed time courses of membrane potential shifts from the data set of DNDS/STX or DNDS/KT5823. We introduced the Hill-type formula as a parametric expression of the time course since most feedforward biochemical signals show a monotonic increase. The cellular variability in this framework can be modeled as the probability distributions of the parameters, which is approximated with the Gamma distributions. We estimated the optimized hyper-parameters in the Gamma distributions for all pharmacological conditions in which the posterior distributions are maximized. The difference in the hyper-parameters between the STX condition and the KT5823 condition suggests that there exists an interaction between the cascades that regulate the NaC and ClC.
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