Biomedical Engineering Reference
In-Depth Information
weakly connected regions. Until recently, this mechanism had not been tested ex-
perimentally (see Sect.
24.4.2
).
24.4.2 Phased Differential Growth as a Mechanism for Cortical
Folding
The ferret is a popular animal for studies of cortical folding, as the ferret brain does
not begin to fold until after birth (Smart and McSherry,
1986a
,
b
; Barnette et al.,
2009
). To test the axonal tension hypothesis, we used tissue dissection to determine
stress patterns in the folding ferret brain. The results indicate that axonal tension
is significant, but the principal directions of this tension (and the corresponding
axon orientations) are different from those predicted by the axon tension hypothesis
(Fig.
24.5
B
;Xuetal.,
2010b
). Notably, there is no significant tension between the
walls of the outward folds (gyri). This result suggests that, although axonal tension
is present, it likely does not play the mechanistic role during folding proposed by
Van Essen (
1997
).
Next, we proposed a new model for folding driven by differential growth. This
model is similar to that of Richman et al. (
1975
) with the following exceptions:
(i) Tangential growth in the cortex is out of phase between adjacent regions (phased
differential growth); and (ii) the underlying subplate grows in response to the de-
veloped stresses. During the simulation, growth in one region produces an outward
fold, which is then followed by a second growth-induced fold in the neighboring re-
gion, and so on (Fig.
24.5
C). Consistent with this idea, imaging studies have shown
that folds form in such a sequential manner during development (Neal et al.,
2007
;
Kroenke et al.,
2009
). This model yields folding geometry and stress distributions
that agree well with experimental results (Xu et al.,
2010b
). More recent data sug-
gest, however, that the differential growth hypothesis may require further refinement
to include a radial gradient in growth (Reillo et al.,
2011
).
24.5 Conclusions
In summary, results from a number of laboratories are providing new insights into
the biomechanical mechanisms of brain morphogenesis. Careful consideration must
be taken in interpreting the results from these studies, as brain morphology can be
highly variable between different model organisms.
The treatment of the subject here is not exhaustive and much work remains to be
done to fill in the gaps. Notably, we have omitted discussion of secondary vesicle
generation in the brain tube, as well as secondary cortical folding. Deeper questions
remain relatively unexplored, such as the possible role of mechanical feedback in
driving and potentiating brain morphogenesis. Indeed, mounting evidence suggests
that the neuroepithelium can actively respond to changes in mechanical stress (Filas
