Is the structure of the brain due to mechanical instabilities or Morphogenesis?

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It has been reported that scientists have used data for various species, and plotted the area of cortex times the square root of its thickness versus of the exposed area of the brain.  All the data points fell on a single universal curve this showed that the combination of total area and thickness grew with the exposed outer area raised to the power 1.25—just as the area of a circle grows with its radius raised to the power 2.  This universal relationship is the same one that describes crumpled paper.  It is thought this is due to the cortex settling into the configuration of least mechanical energy.  B Mota and S Herculano-Houzel 2015.

This shape might also endow some other useful qualities e.g In the case of graphene, it has been found that porous and highly crumpled graphene structure with a large surface area and pore volume facilitates fast ionic transport within the electrode while preserving electrical conductivity and electrochemical properties.  Jun Yan et al 2013.

Studies have emphasized the importance of differential growth and mechanical stress in shaping the morphology of multicellular organisms and tissues.  Patterning in airways, arteries, skin, and gut epithelium have all been associated with mechanical instabilities.
However one of the most studied step in the morphogenesis of metazoans is gastrulation which corresponds to a symmetry breaking of the spherical embryo and an invagination. The origin of this folding remains unknown even if mechanical factors are undoubtedly implied. Different mechanical actions (constriction, contraction, traction, gel swelling) can lead to similar shapes of the sea urchin primary gastrula.  In these conditions it raises the issue of realistic modeling of far more complex buckling processes such as the gyrification of mammal brains.   Julien Lefèvre et al (2010) have suggested a similarity between turing patterns and brain gyri and sulci, and proposed to model the cortical anatomy as obtained by a reaction-diffusion mechanism. 

These findings leave the question of whether such self organisation is due to mechanical instabilities or biochemical morphogenesis.   Some have met this through suggesting a combined approach. 

The mechanical stress patterns that would produce brain folding if it were due to bulging or bending are not compatible with those observed in real brains (Xu et al., 2009, 2010). Recent evidence suggest that brain folding is more likely the result of a buckling instability induced by global neocortical growth……The intrinsic "energy for refinement" could well be both biological and mechanical.  O Foubet et al 2015.

In self-organization, the external system may support the operation of the internal system by providing permissive conditions (such as supporting cell growth evenly), but should not give ‘biased’ information to the cells for patterning. Yoshiki Sasai 2012.

In the case of optic cup self organisation, Complex morphogenesis, seems to be driven by a sequential execution of local mechanical rules, each of which is relatively simple.  Surrounded by the stiff RPE, the expanding soft tissue of the neural retina cannot extend the hard outer shell, but instead has to deform itself by buckling inwards. On the basis of these observations, a relaxation–expansion model has been suggested for self-driven optic-cup morphogenesis. This model does not depend on external forces or extrinsic physical constraints, but involves only three sequential rules of local mechanical changes.

A similar self-organizing phenomenon, has been reported for multilayered cerebral cortex formation from mouse and human ES cells and from induced pluripotent stem (iPS) cells. 

But optic-cup invagination could be regulated more precisely in space and time when both optic-cup self-organization (internal rules) and spatial constraints owing to lens invagination and cornea formation (external influences) are cooperatively coupled..  Yoshiki Sasai 2012. 

Is this one of those cases where one side is obviously right and the other wrong - or does a combined approach offer a more fruitful way forward?



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Since I wrote this post the following research has been published.

Zhen Ma et al 2015 have used PEG-patterned substrates to geometrically confine human pluripotent stem cell colonies and spatially present mechanical stress. Modulation of the WNT/β-catenin pathway promoted spatial patterning via geometric confinement of the cell condensation process during epithelial–mesenchymal transition, forced cells at the perimeter to expressed an OCT4+ annulus, which is coincident with a region of higher cell density and E-cadherin expression. The biochemical and biophysical cues synergistically induced self-organizing lineage specification and the creation of a beating human cardiac microchamber confined by the pattern geometry.