Computational modeling of pathological layer formation in neurodevelopmental disorders

Abstract

Event Abstract Back to Event Computational modeling of pathological layer formation in neurodevelopmental disorders Roman Bauer1* and Marcus Kaiser1 1 Newcastle University, United Kingdom The mammalian cortex is composed of six main cell layers with distinct form and function. This laminar structure is the result of a complex developmental process, which is implicitly specified in the genetic code, but contingent upon extracellular factors. Computational modeling provides a valuable approach for a better understanding of this dynamic process [1]. Here, we present a computer model to put in comparison the development of normal and pathological laminar organization. In particular, we investigated scenarios where the migration of certain cells does not take place properly, such as for example in the neurodevelopmental disease periventricular heterotopia (PH) [2]. In PH, certain neurons that have failed to migrate into the developing cerebral cortex remain as nodules or neurons that line the ventricular surface. To implement our model we used the software framework Cx3D [3], which is a software framework for simulations of neural development in 3D physical space. Based on this model, we simulate a gene regulatory network, which by differentiation, proliferation and migration of cells gives rise to a laminated structure. By introducing defects to our artificial genetic code, our simulations yield results that are in good accordance with experimental observations. Overall, our results constitute a comprehensive model for the laminar disorganization in PH, which can also be applied to better understand many other neurodevelopmental trajectories of brain disorders. Acknowledgements This work was supported by the Engineering and Physical Sciences Research Council of the United Kingdom (EP/K026992/1) as part of the Human Brain Development Project (http://www.greenbrainproject.org/) References [1] Zubler, F., Hauri, A., Pfister, S., Bauer, R., Anderson, J. C., Whatley, A. M., & Douglas, R. J. (2013). Simulating cortical development as a self constructing process: a novel multi-scale approach combining molecular and physical aspects. PLoS Comput Biol, 9(8), e1003173. [2] Fox, J. W., Lamperti, E. D., Ekşioğlu, Y. Z., Hong, S. E., Feng, Y., Graham, D. A., ... & Berkovic, S. F. (1998). Mutations in filamin 1 prevent migration of cerebral cortical neurons in human periventricular heterotopia. Neuron, 21(6), 1315-1325. [3] Zubler, F., & Douglas, R. (2009). A framework for modeling the growth and development of neurons and networks. Frontiers in computational neuroscience, 3, 25. Keywords: computational modeling, gene regulatory networks (GRN), layer formation, neurodevelopmental diseases, Subcortical heterotopia Conference: Neuroinformatics 2016, Reading, United Kingdom, 3 Sep - 4 Sep, 2016. Presentation Type: Poster Topic: Computational neuroscience Citation: Bauer R and Kaiser M (2016). Computational modeling of pathological layer formation in neurodevelopmental disorders. Front. Neuroinform. Conference Abstract: Neuroinformatics 2016. doi: 10.3389/conf.fninf.2016.20.00065 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 30 Apr 2016; Published Online: 18 Jul 2016. * Correspondence: Dr. Roman Bauer, Newcastle University, Newcastle upon Tyne, United Kingdom, r.bauer@surrey.ac.uk Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Roman Bauer Marcus Kaiser Google Roman Bauer Marcus Kaiser Google Scholar Roman Bauer Marcus Kaiser PubMed Roman Bauer Marcus Kaiser Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.