Poster No:
1300 WTh-PM
Authors:
Monica Hurdal1, Deborah Striegel1
Institutions:
1Department of Mathematics, Florida State
University, Tallahassee, FL
Introduction:
Cortical folding patterns vary widely across species in
terms of the number and location of folds. No consensus has been reached
to explain cortical morphogenesis. Current hypotheses are mechanistic
(Van Essen, 1997) and cellular (Noctor et al., 2004). We adopt the
intermediate progenitor (IP) model hypothesis (Kriegstein et al., 2006)
and present a mathematical model to offer a possible explanation as to
the location of cortical fold formation.
During cortical
development, a proliferative layer of cells lines the lateral ventricle
(LV), called the ventricular zone (VZ). Radial glial cells in the VZ are
activated to create subsets of IP cells which create a local neuron
amplification, resulting in gyrus formation. We use a Turing
reaction-diffusion system (Turing, 1957) to model cortical folding
pattern formation. This model offers an explanation as to why certain
species may have little or no folding and it is able to predict the
consistency in pattern formation across species.
Methods:
Turing systems have been used to study pattern formation in
many biological applications, including bacteria (Varea et al., 1999)
and animal coat patterns (Murray, 2003). A Turing system is a
reaction-diffusion system of two chemical morphogens representing an
activator and an inhibitor. The biological basis of our model is that
chemical morphogens may be governed by specific genes to regulate IP
cell production. The LV and the VZ are key components in the IP model
hypothesis of cortical pattern formation. We model the shape of the LV
with a prolate spheroid and the VZ with a prolate spheroidal surface.
The major axis of the prolate spheroid corresponds to the major axis of
the lateral ventricle (Striegel and Hurdal, 2009). The focal distance of
the prolate spheroid models the eccentricity of the LV. We discretized
the Turing system and used periodic boundary conditions to carry out
numerical simulations to study the role of domain scaling on the arising
pattern.
Results:
We have developed a formula that enables pattern formation
to be predicted on a prolate spheroid domain by relating a given domain
scale and domain shape to the arising pattern. This pattern is indicated
by the spheroidal indices (m,n). Given a two tone color gradient such
as black to copper, m corresponds to the number of copper (or black)
spots traversing φ (where φ is the rotation term of the prolate
spheroid) and n corresponds to m plus the number of shifts from copper
to black (or black to copper) traversing θ (where θ is the asymptotic
angle with respect to the prolate spheroid major axis) for a fixed φ.
Copper regions can be considered to be activated regions and black
regions are non-activated regions. Sectorial curves are formed when the
spheroidal harmonic indices are equal. For example (m,n) = (1,1) forms
one sectorial curve, (2,2) forms two sectorial curves, etc. Transverse
curves are formed for spheroidal harmonic indices (0,n) for n even. For
example, (0,2) forms one transverse curve, (0,4) forms two transverse
curves, etc. Examples of transverse and sectorial curves are shown in
Figure 1.
Prolate spheroidal harmonics may be characterized in
terms of cortical sulci. Sectorial sulci in the brain correspond to
sulci that extend from the frontal lobe around the Sylvian fissure to
the temporal lobe, matching the direction of the major axis of the
prolate spheroid approximating the LV. Examples include the calcarine
and cingulate sulci. Transverse sulci correspond to rings around the VZ.
Examples include the central and precentral sulci.
Our
simulations revealed that increasing the focal distance changed the
order in which transverse and sectorial curves formed. For smaller focal
distances, a sectorial curve is formed first. As focal distance
increases, then as the domain scaling increases a transverse curve forms
before the first sectorial curve. Greater increases in focal distance
result in two transverse curves forming before a sectorial curve.
Conclusions:
Our model illustrates how sulcal placement and
directionality are related to changes in focal distance. We observed
that as focal distance increased, the order of transverse and sectorial
curves changed. Thus, focal distance affects the order in which curves,
and hence sulci, are formed. One interpretation of these results relates
to evolution. Earlier in an evolutionary timeline when the LV focal
distances are smaller, the first transverse sulcus appears. Later when
the focal distances are larger, a second transverse sulcus appears. Many
species exhibit these sulcal formation patterns. Thus, we are able to
predict cortical patterns that correlate with cortical observations. Our
model is able to capture global shape characteristics of the cortex and
it can link the evolutionary development of cortical sulcal formation
to the eccentricity of the lateral ventricle. This model represents an
important step in improving our understanding of cortical folding
pattern formation of the brain.
References:
Kriegstein, A. (2006), 'Patterns of Neural Stem and
Progenitor Cell Division may Underlie Evolutionary Cortical Expansion', Nat
Rev Neurosci, vol. 7, pp. 883-890.
Murray, J.D. (2003), Mathematical
Biology II: Spatial Models and Biomedical Applications.
Noctor,
S.C. (2004), 'Cortical Neurons Arise in Symmetric and Asymmetric
Division Zones and Migrate through Specific Phases', Nat Neurosci,
vol. 7, pp. 136-144.
Striegel, D.A. (2009), 'Chemically Based
Mathematical Model for Development of Cerebral Cortical Folding
Patterns', PLoS Comput Biol, vol. 5, pp. e1000524.
Turing,
A.M. (1957), 'The Chemical Basis of Morphogenesis', Philos T R Soc
Lond, B, vol. 237, pp. 37-72.
Van Essen, D.C. (1997), 'A
Tension-based Theory of Morphogenesis and Compact Wiring in the Central
Nervous System', Nature, vol. 385, pp. 313-318.
Varea, C.
(1999), 'Turing Patterns on a Sphere', Phys Rev E, vol. 60, pp.
4588-4592.
Categories
- Classification and Predictive Modeling
(Modeling and Analysis)
- Anatomical Studies (Neuroanatomy)