Journal article
How neurons migrate: a dynamic in-silico model of neuronal migration in the developing cortex
BMC Systems Biology, Vol.5
Sep/2011
Abstract
Background: Neuronal migration, the process by which neurons migrate from their place of origin to their final position in the brain, is a central process for normal brain development and function. Advances in experimental techniques have revealed much about many of the molecular components involved in this process. Notwithstanding these advances, how the molecular machinery works together to govern the migration process has yet to be fully understood. Here we present a computational model of neuronal migration, in which four key molecular entities, Lis1, DCX, Reelin and GABA, form a molecular program that mediates the migration process. Results: The model simulated the dynamic migration process, consistent with in-vivo observations of morphological, cellular and population level phenomena. Specifically, the model reproduced migration phases, cellular dynamics and population distributions that concur with experimental observations in normal neuronal development. We tested the model under reduced activity of Lis1 and DCX and found an aberrant development similar to observations in Lis1 and DCX silencing expression experiments. Analysis of the model gave rise to unforeseen insights that could guide future experimental study. Specifically: (1) the model revealed the possibility that under conditions of Lis1 reduced expression, neurons experience an oscillatory neuron-glial association prior to the multipolar stage; and (2) we hypothesized that observed morphology variations in rats and mice may be explained by a single difference in the way that Lis1 and DCX stimulate bipolar motility. From this we make the following predictions: (1) under reduced Lis1 and enhanced DCX expression, we predict a reduced bipolar migration in rats, and (2) under enhanced DCX expression in mice we predict a normal or a higher bipolar migration. Conclusions: We present here a system-wide computational model of neuronal migration that integrates theory and data within a precise, testable f
Details
- Title
- How neurons migrate; a dynamic in-silico model of neuronal migration in the developing cortex
- Creators
- Yaki Setty (null)Chih-Chun Chen (null)Maria Secrier (null)Nikita Skoblov (null)Dimitrios Kalamatianos (null)Stephen Emmott (null)
- Resource Type
- Journal article
- Publication Details
- BMC Systems Biology, Vol.5; Sep/2011
- Number of pages
- 13
- Language
- English
- DOI
- https://doi.org/10.1186/1752-0509-5-154
- Grant note
- European Research Council (ERC) under EU; National Biophotonics and Imaging Platform Ireland; Irish GovernmentWe wish to thank Orly Reiner and David Harel from the Weizmann Institute of Science for suggesting neuronal migration as a modeling subject and Hillel Kugler, Matthew Smith and Neil Dalchau of the Computational Science Laboratory at Microsoft Research for helpful discussions and comments. We would also like to thank Ken Duffy and Jeannette Valency for proofreading and correcting the manuscript thoroughly. This research was supported in part by an Advanced Research Grant from the European Research Council (ERC), under the EU's 7th Framework and through the National Biophotonics and Imaging Platform Ireland, funded by the Irish Government's Programme for Research in Third Level Institutions, Ireland's EU Structural Funds Programmes 2007 - 2013._ALMAME_DELIMITER_
- Scientific Unit
- The Weizmann Institute of Science
- Record Identifier
- 993262705903596
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