Computational models of mouse neural progenitors

During cortical development, neural progenitor cells divide either symmetrically or asymmetrically into proliferative and postmitotic neural cells. Although the precise mechanisms of neurogenesis remains elusive, cell behavior and spacial position in the germinal zones have been postulated to influence cell fate decision.

We address the task of modeling cell migration and differentiation using computational models. In contrast to conventional mathematical models, computational models present a recipe – an algorithm – for an abstract execution engine to mimic a design or natural phenomenon. Such models have successfully been used to qualitatively describe biochemical processes.

In this work group, we analyze interkinetic nuclear migration (the apical–basal movement of dividing cells) and the relationship of this cell behavior with the cell cycle regulation. The goal is to produce a mechanistic model that can explain the data recorded by Colette Dehay team.

Workgroup organization

• Introduction on cortical development: focus on cell division and migration
• Tutorial on computational models
• Short introduction (if required) on Java scripting with Processing
• Programming group focused on the implementation of cell migration in a simulation software and analysis of recorded data

Reading

• Colette Dehay & Henry Kennedy, Cell-cycle control and cortical development, Nature Reviews Neuroscience 8, 438-450 (June 2007)  http://www.nature.com/nrn/journal/v8/n6/full/nrn2097.html
• Jasmin Fisher & Thomas A Henzinger, Executable cell biology, Nature Biotechnology 25, 1239 - 1249 (2007)  http://www.nature.com/nbt/journal/v25/n11/abs/nbt1356.html
• Yoichi Kosodo et al, Regulation of interkinetic nuclear migration by cell cycle-coupled active and passive mechanisms in the developing brain, The EMBO Journal (2011) 30, 1690 - 1704  http://www.nature.com/emboj/journal/v30/n9/abs/emboj201181a.html

Links

• Download Cortex3D, a tool for simulating the growth of cortex in 3D  http://www.ini.uzh.ch/~amw/seco/cx3d/
• Download Processing 1.5  http://processing.org/

Meeting summaries

Kick-off meeting (Tuesday, 3rd of March 2011)

• Introduction on cortical development
  • Marion explained basic principle of cortical development of the mouse cerebral cortex (see suggested readings)
  • Elodie presented a more focused introduction in the regulation of cell proliferation and cell migration, specifically interkinetic nuclear migration (INM)

• Introduction in computational models
  • Sabina gave a brief description of different computational models that can be used to qualitatively model biological processes (see suggested readings)
  • Sabina showed how computational models have been used in the literature to analyze INM mechanisms (see suggested readings) and an example of implementation in Processing

Programming group (Wednesday, 4th of March 2011)

Goal of this group is to use simulation tools (Processing, Cortex3D) to analyze the mechanisms (physical and molecular) that regulate INM. We want to address the following questions:

• Is the migration during the G1 cell cycle phase an active or passive mechanism?
• What is the relationship between cell cycle regulation and speed of migration?

We implemented the simulation into two different simulation environments:

• Processing (2D simulation)
• Cortex3D (3D simulation)

Discussion group (Thursday, 5th of March 2011)

• Introduction on cortical development
  • Marion explained the differences in cortical development between mouse and monkey and in the migration routes taken by inhibitory cells

• Simulation
  • Elodie and Fred succesfully implemented the INM in Cortex3D, where they can test how different parameters (speed, collision, friction, cell cycle phases) affect the behaviour of neural precursors.