490
8 Morphogenesis
Consistent with measured distributions of actin, phosphorylated myosin, and cell
proliferation, cell wedging is simulated in defined areas on the dorsal and ventral
sides of the bud region, while axial growth is specified in the bud and adjacent
(distal) regions (Fig. 8.71a–c). With these experimentally based mechanisms, a bud
forms on the dorsal side of the tube (Fig. 8.71c). The predicted morphology is
most realistic when both apical contraction and axial growth are included (compare
Figs. 8.70b and 8.71d).
8.9 Mechanical Regulation of Morphogenesis
Except for growth laws used in some models for brain development, all models for
morphogenesis considered thus far specify growth and contraction as functions of
position and time. This approach tacitly assumes that genes control all aspects of
morphogenesis, with the cellular machinery merely following orders.
Indeed, for many decades, the prevailing view among most biologists was that
embryonic development is controlled entirely by genetic and chemical factors,
although some recognized that mechanical forces are needed to physically construct
an embryo. Mounting evidence now suggests, however, that feedback from the
mechanical environment (e.g., stress and strain) also plays a role in regulating
morphogenesis. Although genes may issue general instructions for cells to follow,
these instructions may need tweaking when environmental conditions change or
something goes wrong. Perturbations could be detected by sensing abnormal stress
or cell shape. The idea that morphogenesis is controlled in part by mechanics
is certainly not new (Thompson 1942), and interest in this subject is increasing
(Patwari and Lee 2008; Mammoto et al. 2013).
In a seminal study, Pouille et al. (2009) examined the behavior of mutant
Drosophila embryos that fail to undergo invagination associated with gastrulation
because they lack the gene Snail. Remarkably, these investigators found that
using a needle to temporarily indent these mutated embryos at a critical time and
location triggers normal invagination. In other words, a mechanical perturbation
can sometimes rescue morphogenesis in embryos lacking the genes that otherwise
are required for normal development.
Pouille et al. (2009) also conducted experiments to determine how indentation
activates this response at the cell level. Their results indicate that the protein
Fog normally recruits myosin to the apical surface of the cells, setting up the
contraction that drives invagination. In Snail mutants, however, cell membranes
invaginate locally (endocytose) to transport Fog into the cytoplasm, where it cannot
participate in apical contraction. Indentation generates membrane tension that
prevents endocytosis, allowing contraction and gastrulation to occur.
Here, we consider a theory espoused by the developmental biologist
L.V. Beloussov, who spent four decades studying morphomechanical feedback
8 Morphogenesis
Consistent with measured distributions of actin, phosphorylated myosin, and cell
proliferation, cell wedging is simulated in defined areas on the dorsal and ventral
sides of the bud region, while axial growth is specified in the bud and adjacent
(distal) regions (Fig. 8.71a–c). With these experimentally based mechanisms, a bud
forms on the dorsal side of the tube (Fig. 8.71c). The predicted morphology is
most realistic when both apical contraction and axial growth are included (compare
Figs. 8.70b and 8.71d).
8.9 Mechanical Regulation of Morphogenesis
Except for growth laws used in some models for brain development, all models for
morphogenesis considered thus far specify growth and contraction as functions of
position and time. This approach tacitly assumes that genes control all aspects of
morphogenesis, with the cellular machinery merely following orders.
Indeed, for many decades, the prevailing view among most biologists was that
embryonic development is controlled entirely by genetic and chemical factors,
although some recognized that mechanical forces are needed to physically construct
an embryo. Mounting evidence now suggests, however, that feedback from the
mechanical environment (e.g., stress and strain) also plays a role in regulating
morphogenesis. Although genes may issue general instructions for cells to follow,
these instructions may need tweaking when environmental conditions change or
something goes wrong. Perturbations could be detected by sensing abnormal stress
or cell shape. The idea that morphogenesis is controlled in part by mechanics
is certainly not new (Thompson 1942), and interest in this subject is increasing
(Patwari and Lee 2008; Mammoto et al. 2013).
In a seminal study, Pouille et al. (2009) examined the behavior of mutant
Drosophila embryos that fail to undergo invagination associated with gastrulation
because they lack the gene Snail. Remarkably, these investigators found that
using a needle to temporarily indent these mutated embryos at a critical time and
location triggers normal invagination. In other words, a mechanical perturbation
can sometimes rescue morphogenesis in embryos lacking the genes that otherwise
are required for normal development.
Pouille et al. (2009) also conducted experiments to determine how indentation
activates this response at the cell level. Their results indicate that the protein
Fog normally recruits myosin to the apical surface of the cells, setting up the
contraction that drives invagination. In Snail mutants, however, cell membranes
invaginate locally (endocytose) to transport Fog into the cytoplasm, where it cannot
participate in apical contraction. Indentation generates membrane tension that
prevents endocytosis, allowing contraction and gastrulation to occur.
Here, we consider a theory espoused by the developmental biologist
L.V. Beloussov, who spent four decades studying morphomechanical feedback