A mathematical model of granule cell generation during mouse cerebellum development Journal Article


Authors: Leffler, S. R.; Legué, E.; Aristizábal, O.; Joyner, A. L.; Peskin, C. S.; Turnbull, D. H.
Article Title: A mathematical model of granule cell generation during mouse cerebellum development
Abstract: Determining the cellular basis of brain growth is an important problem in developmental neurobiology. In the mammalian brain, the cerebellum is particularly amenable to studies of growth because it contains only a few cell types, including the granule cells, which are the most numerous neuronal subtype. Furthermore, in the mouse cerebellum granule cells are generated from granule cell precursors (gcps) in the external granule layer (EGL), from 1 day before birth until about 2 weeks of age. The complexity of the underlying cellular processes (multiple cell behaviors, three spatial dimensions, time-dependent changes) requires a quantitative framework to be fully understood. In this paper, a differential equation-based model is presented, which can be used to estimate temporal changes in granule cell numbers in the EGL. The model includes the proliferation of gcps and their differentiation into granule cells, as well as the process by which granule cells leave the EGL. Parameters describing these biological processes were derived from fitting the model to histological data. This mathematical model should be useful for understanding altered gcp and granule cell behaviors in mouse mutants with abnormal cerebellar development and cerebellar cancers.
Keywords: mice; morphology; medulloblastoma; proliferation; sonic hedgehog; differentiation; growth; differential; homeobox; insights; equations; vermis; granule cell precursor cells; external granule layer; egl
Journal Title: Bulletin of Mathematical Biology
Volume: 78
Issue: 5
ISSN: 0092-8240
Publisher: Springer  
Date Published: 2016-05-01
Start Page: 859
End Page: 878
Language: English
ACCESSION: WOS:000377933900001
DOI: 10.1007/s11538-016-0163-3
PROVIDER: wos
PMCID: PMC4911999
PUBMED: 27125657
Notes: Article -- Source: Wos
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  1. Emilie Legue
    7 Legue
  2. Alexandra L Joyner
    97 Joyner