Biomedical Engineering Reference
In-Depth Information
is concentrated on the basal side of these cells, consistent with actomyosin driven
basal contraction. (Interestingly, in most other instances of invagination that involve
cytoskeletal contraction, the contraction occurs at the cell apex, Davies,
2005
.) In
embryos that lack laminin, which is a major component of the basement membrane
surrounding the outside (basal side) of the brain tube, the mid-hindbrain bound-
ary still forms, but is not as sharp as in wild type embryos (Gutzman et al.,
2008
).
Hence, differential lumen opening may set the initial pattern for the brain vesicles,
while ongoing actomyosin activity remodels the tube into its characteristic three-
dimensional structure.
Outside of zebrafish, however, the mechanisms of brain vesicle formation have
received relatively little attention. To begin exploring this process, we measured
morphogenetic strains at the inner wall of the neural tube during the stages of vesi-
cle formation in the chicken embryo (Filas et al.,
2008
). As expected, negative cir-
cumferential strains occur at the mid-hindbrain boundary, with negative longitudi-
nal strains in the surrounding ventricles. These results suggest that the brain may
shorten in a specific, regionally dependent manner to facilitate vesicle formation.
Corresponding changes in mechanical properties were measured by probing the
stiffness of the neuroepithelium via microindentation (Xu et al.,
2010a
). Surpris-
ingly, the characteristic brain geometry gives a nearly uniform indentation stiffness
along the brain tube.
Recently, we have developed a finite element model for brain vesicle formation
(BAF unpublished). The model consists of a circular tube with contraction simulated
within a narrow region next to the lumen. When the mid-hindbrain boundary region
undergoes circumferential contraction and the surrounding vesicles isotropic con-
traction (consistent with actin staining), the model yields geometric changes consis-
tent with experimental measurements (Fig.
24.4
B).
Extrinsic forces also may play a role in shaping the brain tube. The brain forms
on the dorsal side of the embryo surrounded by a loosely packed network of cells
and extracellular matrix known as the head mesenchyme. During vesicle forma-
tion in chicken and human embryos, the early brain seals at both ends to become a
fluid-filled pressure vessel. The brain then begins a period of rapid expansion, and
studies have shown that this growth depends on cerebrospinal fluid pressure (Gato
and Desmond,
2009
). Specifically, prematurely sealing the brain cavity causes the
expansion to begin early (Desmond and Levitan,
2002
), whereas relieving the pres-
sure severely retards growth (Desmond and Jacobson,
1977
).
In these embryos, however, the majority of vesicle morphogenesis occurs prior
to the brain becoming a sealed, pressurized system. Hence, the primary source of
external forces acting on the neuroepithelium during vesicle formation would likely
be from surrounding tissues. To explore these effects, we removed the head mes-
enchyme and cultured isolated chicken brains through the stages of vesicle forma-
tion (Filas et al.,
2011
). In these brain tubes, the vesicles and overall morphology
developed normally, suggesting that vesicle formation is intrinsic to the neuroep-
ithelium.
