Neuronal Morphogenesis

My work on biological pattern formation is focused on neuronal morphogenesis, and involves an international collaboration between the Department of Physics, Emory University and the Dalhousie University Medical School in Canada. With Professor Alan Fine we are investigating the growth of neurons and and attempting to relate the observed structure to the dynamics of curved interfaces. We are performing massively parallel simulations of geometric interfacial growth models which obey the biological constraints known to apply in real neuronal growth.

Gradients of intracellular ions in in developing neurites. Sodium concentration in a growing model neuron (A) increases distally along neurites in concert with membrane depolarization. Calcium concentration in the same neuron (B), influenced by membrane potential, is also higher along the neurite than within the cell body, much like calcium gradients in real growing neurons

We are concentrating at present on dendritic branching and axonal differentiation during neuronal growth, and especially on the calcium ion as a possible morphogen catalysing cytoskeletal polymerization and depolymerization processes. We describe the growth of cells under the control of such diffusible factors, whose local concentrations resulted from diffusive influx and active extrusion across an excitable cell membrane. Linear stability analysis indicates that diffusion-controlled growth of spherical shapes will be unstable if the membrane permeability to these factors is voltage-gated. Explicit numerical integration of the equations governing this growth lead to the emergence of dendritic forms in a manner that mirrors the development of living cells, with complex branching patterns influenced by membrane conductance, galvanotropism and chemotropism.

Related Publications

H.G.E. Hentschel and Alan Fine, Instabilities in Cellular Dendritic Morphogenesis. Phys. Rev. Lett. 73, 3592 (1994).

H.G.E. Hentschel and Alan Fine, Diffusion-Regulated Control of Cellular Dendritic Morphogenesis. Proceedings of the Royal Society B263, 1 (1996).

D.C. Samuels, H.G.E. Hentschel and Alan Fine, Parallel Simulations of Neuron Growth. Computers in Physics, 10, 129 (1996).

D.C. Samuels, H.G.E. Hentschel and Alan Fine,The Origin of Neuronal Polarization: A Model of Axon Formation. Phil. Trans. R. Soc. B351, 1147 (1996).

H.G.E. Hentschel and Alan Fine, The Influence of Intracellular Transport on Axonal Development. Proceedings of the MRS 1997 Fall Meeting in Symposium K: Material Science of the Cell, 489, 181 (1998).

H.G.E. Hentschel, Alan Fine and D.C. Samuels, Instabilities During the Dendritic and Axonal Development of Neuronal Form. Physica A 254, 46 (1998).