Biomedical Engineering Reference
In-Depth Information
Fig. 24.3
Model for lumen opening. (
A
) Finite element model of a tube with a slit-like cross sec-
tion. Tangential contraction is prescribed at the apical (inner wall) at two mediolateral (
darkened
)
locations. (
B
) Local contraction generates lateral hinge points (
asterisks
) and opens the lumen into
a
diamond shape
. Figure adapted from Filas et al. (
2012
), with permission from Biomechanics and
Modeling in Mechanobiology
(Filas et al.,
2012
); see also Fig. 5G, J, M in Lowery and Sive (
2005
). It is currently
unclear whether all regions initially open as diamonds (as occurs in the midbrain;
Nyholm et al.,
2009
) and later remodel into different shapes, or if the shape inhomo-
geneities are preserved throughout the opening process. Moreover, the significance
of regionally varying shapes along the length of the brain tube is not yet known. No-
tably, at comparable developmental stages, early chicken, mouse, and human brains
are generally round in transverse cross section (Fig.
24.2
B, Copp et al.,
2003
; Filas
et al.
2011
,
2012
).
The morphogenetic mechanisms that drive luminal opening in the zebrafish mid-
brain are beginning to be uncovered. In particular, inhibiting myosin by blebbistatin
exposure prevents this process (Nyholm et al.,
2009
). This result has led to spec-
ulation that cytoskeletal contraction at lateral hinge points may facilitate luminal
opening in zebrafish (Nyholm et al.,
2009
). Consistent with this idea, finite element
modeling has shown that simulating local contraction at the inner wall of a tube
with an initially slit-like cross section generates lateral hinge points and a diamond-
shaped lumen (Fig.
24.3
).
Once the lumen opens, later expansion of the hindbrain requires relaxation of
the cytoskeleton (Gutzman and Sive,
2010
). Hence, it seems that the zebrafish brain
tube actively contracts to establish a lumen, and later relaxes to facilitate expansion
in response to increasing fluid pressure in the lumen (see Sect.
24.3.2
).
24.3.2 Brain Vesicle Formation
Evidence suggests that brain tube morphology at the mid-hindbrain boundary in ze-
brafish is not purely a consequence of differential luminal expansion. The decreased
radius in this region is associated with wedge-shaped cells produced by a com-
bination of basal constriction and apical expansion (Gutzman et al.,
2008
). Actin
