Physics and the canalization of morphogenesis: a grand challenge in organismal biology

Abstract

Morphogenesis takes place against a background of organism-to-organism and environmental variation. Therefore, fundamental questions in the study of morphogenesis include: How are the mechanical processes of tissue movement and deformation affected by that variability, and in turn, how do the mechanic of the system modulate phenotypic variation? We highlight a few key factors, including environmental temperature, embryo size and environmental chemistry that might perturb the mechanics of morphogenesis in natural populations. Then we discuss several ways in which mechanics-including feedback from mechanical cues-might influence intra-specific variation in morphogenesis. To understand morphogenesis it will be necessary to consider whole-organism, environment and evolutionary scales because these larger scales present the challenges that developmental mechanisms have evolved to cope with. Studying the variation organisms express and the variation organisms experience will aid in deciphering the causes of birth defects.

Figure 1. Size variation in Xenopus laevis

A) Eggs laid by different females can differ in their diameter. Egg size variation is often overlooked unless two clutches are directly compared side-by-side. A clutch of normal sized eggs (Diameter: 1.42 ± 0.03 mm, mean ± SD) is shown in the left half of the panel, and a clutch of large eggs (1.77 ± 0.02 mm) is shown in the right half panel. B) Early cleavage stages show that the large- and normal-sized eggs can undergo synchronous division cycles. C) Rounds of successful cell division produced late blastula stage embryos with indistinguishable patterns of animal cap ectoderm. D) Subsequent development through gastrulation showed differences in the formation of the bottle cells and closure of the blastopore (large embryo: lower; normal sized: upper). However, once these gastrulation movements advanced the process of neurulation appeared unchanged. E) Large and normal sized embryos appeared to neurulate at the same time. F) As development progressed tadpoles derived from large eggs appeared more similar in length but partition more yolk cells into ventral tissues. G) Size differences in the early "round-embryo" blastula stages were reduced once the body plan was shaped and the embryo elongated. Eggs and embryos in B, C, and E are mixed to highlight difference in size.

Figure 2. A mechanical analogy for robust morphogenesis due to limit point buckling in an elastic tissue

Two hinged beams comprised of either elastic (A) or viscous (B) material will show quite different behavior (C) when loaded by a force (F) along the gray arrow. If one one looks at the position of the central point (lower part of C) after application of a square pulse of force (upper part of C), one gets very different behaviors for the two models. For any force below a critical force, the elastic model (solid black line) will be in the original configuration; above that critical force, the elastic model will snap into a new configuration. The viscous model (dashed lines) can take on any position, depending on both force magnitude and duration (the separate lines) of the pulse.

Figure 3. Normal development can occur despite deformation of the X. laevis embryo

A pair of embryos were filmed in a mirror (A, B, and C) to image development from the side. The same pair of embryos was imaged from above in D. The embryo on the left had the vitelline membrane removed at Stage 8 and slumped under its own weight, but completed gastrulation and neurulation without noticeable defects; the embryo on the right had an intact vitelline membrane and remains round through gastrulation.

Figure 4. Scheme for integrating organism-scale and molecular-scale processes in developmental biomechanics

Processes at the molecular, cellular and tissue scale map stochastic, genetic, and environmental variation onto variation in mechanical variables (including developmental timing and geometry) that drive morphogenesis; the physics of morphogenesis maps the resulting variation into variation in morphology; this in turn is mapped onto variation in performance. The graphs illustrate hypothetical covariances among a few of the variables that might be relevant for Xenopus. Arrows indicate possible instances of feedback (e.g. mechanotransduction, changes in inductive events or geometry at earlier developmental stages, or developmental adaptation). Naturally, not all combinations of factors or connections are shown.