Simulating Cortical Development as a Self Constructing Process: A Novel Multi-Scale Approach Combining Molecular and Physical Aspects

Abstract

Current models of embryological development focus on intracellular processes such as gene expression and protein networks, rather than on the complex relationship between subcellular processes and the collective cellular organization these processes support. We have explored this collective behavior in the context of neocortical development, by modeling the expansion of a small number of progenitor cells into a laminated cortex with layer and cell type specific projections. The developmental process is steered by a formal language analogous to genomic instructions, and takes place in a physically realistic three-dimensional environment. A common genome inserted into individual cells control their individual behaviors, and thereby gives rise to collective developmental sequences in a biologically plausible manner. The simulation begins with a single progenitor cell containing the artificial genome. This progenitor then gives rise through a lineage of offspring to distinct populations of neuronal precursors that migrate to form the cortical laminae. The precursors differentiate by extending dendrites and axons, which reproduce the experimentally determined branching patterns of a number of different neuronal cell types observed in the cat visual cortex. This result is the first comprehensive demonstration of the principles of self-construction whereby the cortical architecture develops. In addition, our model makes several testable predictions concerning cell migration and branching mechanisms.

Unsupervised lineage‐based characterization of primate precursors reveals high proliferative and morphological diversity in the OSVZ

“…Such an adaptive system could allow for self‐organization and thereby provide the plasticity and robustness needed to generate the complexity of the adult cortex (Chang et al, 2008; Huang, 2009; Kennedy and Dehay, 2012; Zubler et al, 2013). …”

Creative destruction: a basic computational model of cortical layer formation

“…Along those lines, other computational studies that model axonal and dendritic trees do not focus on the origins of a layered architecture (Koene et al 2009;Cuntz et al 2010). In contrast, Zubler et al present an agent-based computational model for cortical lamination with mechanical interactions (Zubler et al 2013). Based on this approach and software (Zubler 2009), cortical development has been studied from a conceptual perspective of selfconstruction and put in correspondence with genetic data (Zubler et al 2013).…”

“…In contrast, Zubler et al present an agent-based computational model for cortical lamination with mechanical interactions (Zubler et al 2013). Based on this approach and software (Zubler 2009), cortical development has been studied from a conceptual perspective of selfconstruction and put in correspondence with genetic data (Zubler et al 2013). Importantly, this approach relies solely on modelling local information exchange, hence it is maintained the biologically realistic condition that cells can only experience their local 3D environment.…”

“…Here, we build upon the approach of Zubler et al (2013). Going beyond a qualitative assessment, we here provide a computational model that reproduces quantitative measurements of the cortical layer architecture.…”

A Generative Growth Model for Thalamocortical Axonal Branching in Primary Visual Cortex

“…In particular, we assess here developmental rules for axonal arborizations in cat area 17, originating from laminae A of dorsal lateral geniculate nucleus (LGN) of the thalamus. Axonal ramifications in this region are characterized by a high bouton density and extensive arborizations [70] are here due to their morphology referred to as florets. These arborizations must be organized with high precision to preserve the spatial resolution of the associated receptive fields [2] and to enable dense synaptic connections for the ocular dominance columns [28,29].…”