Biomedical Engineering Reference
In-Depth Information
autism, and mental retardation. Morphogenesis offers a number of challenges for
computational modelers, and we hope this review stimulates more interest in these
problems among biomechanical engineers.
24.2 Neurulation and Brain Tube Formation
Neurulation is the earliest stage of development specific to the nervous system. This
process begins within the first three weeks of conception in humans, as a central
region of ectoderm called the neural plate folds to create the neural tube (Fig.
24.1
).
The wall of the tube is a neuroepithelium composed of a single layer of undiffer-
entiated neural progenitor cells (Lowery and Sive,
2009
). The cells are columnar,
and the cell nuclei migrate between the apical side (facing the lumen) and basal side
(facing the exterior) during the cell cycle, giving the neuroepithelium a pseudos-
tratified, or multi-layered appearance (Sauer,
1935
; Miyata,
2008
). Eventually, the
anterior and posterior regions of the neural tube become the brain and spinal cord,
respectively.
Morphogenesis of the neural tube occurs in a specific spatiotemporal pattern
along the length of the embryo. In the chicken, mouse, and human embryo, the neu-
ral plate elevates, folds, and fuses to form a tube with a hollow lumen (Fig.
24.1
A).
Depending on the longitudinal position along the tube, this closure is facilitated by
the formation of one or three hinge points (Fig.
24.1
A, asterisks). Generally, multi-
ple hinge points are present at the anterior end of the tube (prospective brain), while
only one hinge point forms posteriorly (prospective spinal cord). The end result is
a tube that decreases in cross-sectional area from the brain through the spinal cord.
Collectively this folding is known as primary neurulation, which has been shown to
require the coordination of forces intrinsic to the neuroepithelium as well as extrin-
sic forces generated by surrounding tissues (Schoenwolf and Smith,
1990
).
In contrast, during later stages of development, an entirely different mechanism
sculpts the furthest posterior spinal cord region. Here, undifferentiated mesenchy-
mal (loosely connected, highly migratory) cells condense and cavitate to form an
internal lumen in a process known as secondary neurulation (Fig.
24.1
B). Hence,
the anterior brain and spinal cord form via coordinated bending of the neuroep-
ithelium, whereas the posterior end of the spinal cord forms via the agglomeration,
cavitation, and epithelialization of loosely connected cells.
In species such as
Xenopus
(frog) and zebrafish, however, such a difference be-
tween neurulation mechanisms is not immediately apparent (Schmitz et al.,
1993
;
Lowery and Sive,
2004
; Harrington et al.,
2009
). Here, neural precursor cells mi-
grate medially to form a neural keel (Fig.
24.1
C, arrows), intercalate (exchange
neighbors), and remodel to form a slit-like lumen. Interestingly, it remains contro-
versial as to whether the brain forms via a primary or secondary neurulation mode
in these species. Dynamic (time lapse) imaging studies suggest that these cells roll
into a tube, as occurs during primary neurulation, but in doing so, the cells interca-
late and migrate, displaying behaviors more typical of those involved in secondary
