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Fig. 24.2 Mechanisms of brain vesicle formation. ( A ) Differential opening of a slit-like brain tube
is concomitant with primary vesicle formation in frog and fish. Shapes vary in transverse cross
sections between the forebrain ( F ), midbrain ( M ), and hindbrain ( H ). ( B ) Primary brain vesicles
similarly form in species with comparatively open brain tubes, but vesicle shapes are rounded and
relatively homogeneous
colocalize and accumulate at the inner wall of the neuroepithelium at hinge points
(Sadler et al., 1982 ; Lee and Nagele, 1985 ; Kinoshita et al., 2008 ). It is currently
unclear whether hinge point formation acts as a driving or a stabilizing force during
normal neural tube closure (Greene and Copp, 2009 ). Early finite element models
have shown that apical constriction can produce invaginations (Odell et al., 1981 )
and hinge-like morphologies (Clausi and Brodland, 1993 ), but this mechanism war-
rants further study.
24.3 Brain Tube Morphogenesis
The brain tube of vertebrates subsequently subdivides into three primary vesicles
(forebrain, midbrain, and hindbrain) (Fig. 24.2 ). Depending on the species, the brain
vesicles develop from either a hollow tube or a comparatively closed, slit-like tube
(Fig. 24.1 ). This suggests that, as in neurulation, morphogenetic mechanisms driv-
ing vesicle formation may vary between species.
24.3.1 Lumen Opening in Zebrafish Brains
To date, mechanistic studies of brain vesicle formation have been conducted pri-
marily in zebrafish embryos. In this species, the internal lumen of the tube differen-
tially opens to generate the primary vesicles. The lumen of the hindbrain opens first,
followed closely by the midbrain and the forebrain (Lowery and Sive, 2005 ). In-
terestingly, the forebrain, midbrain, and hindbrain lumens open into different cross-
sectional shapes (Fig. 24.2 A). Specifically, the midbrain lumen is shaped like a di-
amond, the hindbrain a triangle, while the forebrain opens into a tear-drop shape
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