8.6 Neural Development
459
contact with the (frictionless) surface ectoderm forces the OV to bend downward
(caudally). To produce dorsal bending, the circumferential growth pattern is changed
so that G θ is greater on the ventral than the dorsal side of the OV. The OV shape at
stage HH13 agrees relatively well with actual morphology (Fig. 8.44c, d).
At stage HH13, the OV is connected to the brain tube through an open segment
called the optic stalk (Fig. 8.44d), which later becomes the optic nerve. This
connection provides open communication between the lumens of the OV and brain
tube, both of which are filled with embryonic cerebrospinal fluid (eCSF). Although
the fluid pressure is only several pascals (Jelinek and Pexieder 1968), relieving this
pressure results in abnormally small eyes (Coulombre 1956). The present model
does not include this effect.
Optic Cup Morphogenesis Experimental studies have provided important clues
about how the optic vesicle transforms into an optic cup. Any hypothesis for OC
formation should be consistent with the following findings:
1. As in most epithelia, actin is located primarily on the apical side of both the
OV and surface ectoderm. This observation is consistent with apical constriction
driving invagination of surface ectoderm to create the LV (see below). However,
the apical side of the OV is its inner surface, apparently ruling out this
mechanism for OV invagination.
2. OV invagination can occur without a forming lens (Hyer et al. 2003), indicating
that the invaginating lens placode does not push the OV (retinal placode) inward.
3. Extracellular matrix gradually accumulates between the OV and surface ectoderm and sticks these layers together by stage HH13 + (Hilfer et al. 1981), just
as the retinal and lens placodes appear (Fig. 8.43). Moreover, the contact area
between the OV and surface ectoderm remains relatively constant during placode
formation, suggesting that the matrix causes local thickening by constraining the
spreading of these growing cell layers (Zwaan and Hendrix 1973; Huang et al.
2011). This idea is also consistent with measurements showing that the matrix is
considerably stiffer than the cells (Oltean et al. 2016).
Considering these observations, Oltean et al. (2016) postulated that matrixconstrained expansion causes the OV to thicken and then invaginate (like growth
of one layer of a bilayered plate, e.g., see Fig. 8.14c). To test this hypothesis, the
authors used an axisymmetric finite-element model. In the initial state, the OV is
approximated by a spherical shell divided into three regions: outer OV, inner OV, and
extracellular matrix (Fig. 8.45a). Transversely isotropic growth (G φ = G θ ; G r = 1)
is specified in the OV, with the inner region growing faster than the outer region; the
matrix does not grow. Based on experimental data, the matrix modulus is set to 50
times that of the OV.
Uniform growth within each region of the OV produces morphology like that
observed in chick embryos (Fig. 8.45b). Besides global shape, comparison of
experimental and numerical results reveal reasonably good agreement for temporal
changes in wall thickness, invagination depth, and curvature at the center of the OC
(Oltean et al. 2016).
459
contact with the (frictionless) surface ectoderm forces the OV to bend downward
(caudally). To produce dorsal bending, the circumferential growth pattern is changed
so that G θ is greater on the ventral than the dorsal side of the OV. The OV shape at
stage HH13 agrees relatively well with actual morphology (Fig. 8.44c, d).
At stage HH13, the OV is connected to the brain tube through an open segment
called the optic stalk (Fig. 8.44d), which later becomes the optic nerve. This
connection provides open communication between the lumens of the OV and brain
tube, both of which are filled with embryonic cerebrospinal fluid (eCSF). Although
the fluid pressure is only several pascals (Jelinek and Pexieder 1968), relieving this
pressure results in abnormally small eyes (Coulombre 1956). The present model
does not include this effect.
Optic Cup Morphogenesis Experimental studies have provided important clues
about how the optic vesicle transforms into an optic cup. Any hypothesis for OC
formation should be consistent with the following findings:
1. As in most epithelia, actin is located primarily on the apical side of both the
OV and surface ectoderm. This observation is consistent with apical constriction
driving invagination of surface ectoderm to create the LV (see below). However,
the apical side of the OV is its inner surface, apparently ruling out this
mechanism for OV invagination.
2. OV invagination can occur without a forming lens (Hyer et al. 2003), indicating
that the invaginating lens placode does not push the OV (retinal placode) inward.
3. Extracellular matrix gradually accumulates between the OV and surface ectoderm and sticks these layers together by stage HH13 + (Hilfer et al. 1981), just
as the retinal and lens placodes appear (Fig. 8.43). Moreover, the contact area
between the OV and surface ectoderm remains relatively constant during placode
formation, suggesting that the matrix causes local thickening by constraining the
spreading of these growing cell layers (Zwaan and Hendrix 1973; Huang et al.
2011). This idea is also consistent with measurements showing that the matrix is
considerably stiffer than the cells (Oltean et al. 2016).
Considering these observations, Oltean et al. (2016) postulated that matrixconstrained expansion causes the OV to thicken and then invaginate (like growth
of one layer of a bilayered plate, e.g., see Fig. 8.14c). To test this hypothesis, the
authors used an axisymmetric finite-element model. In the initial state, the OV is
approximated by a spherical shell divided into three regions: outer OV, inner OV, and
extracellular matrix (Fig. 8.45a). Transversely isotropic growth (G φ = G θ ; G r = 1)
is specified in the OV, with the inner region growing faster than the outer region; the
matrix does not grow. Based on experimental data, the matrix modulus is set to 50
times that of the OV.
Uniform growth within each region of the OV produces morphology like that
observed in chick embryos (Fig. 8.45b). Besides global shape, comparison of
experimental and numerical results reveal reasonably good agreement for temporal
changes in wall thickness, invagination depth, and curvature at the center of the OC
(Oltean et al. 2016).