Cytoskeletal mechanics of neurulation: insights obtained from computer simulations

Abstract

The morphogenetic movements associated with the process of neurulation have been the subject of much investigation during the last one hundred years. A plethora of experimental evidence has been generated regarding the forces that drive this seemingly simple process, and many theories about the mechanics of the process have been proposed. Recent computer simulations have proved useful for evaluating these theories from a mechanical perspective. In this work, computer simulations are used to investigate several theories about the forces that drive neurulation. A simplified version of a formulation previously presented by the authors provides the mathematical foundation for these simulations. The simulations confirm that forces generated by circumferential microfilament bundles (CMB's) in conjunction with notochord forces can produce the rolling motions characteristic of amphibian neurulation. They also support the notion that redundancies exist in the systems of forces available to drive neurulation shape changes. The shape changes that occur following a variety of surgical and teratogenic interventions are also simulated. These simulations corroborate the role of circumferential microfilament bundles as a primary force generator.

Theoretical study of Beloussov’s hyper-restoration hypothesis for mechanical regulation of morphogenesis

“…4c). This behavior suggests that growth (or other deformation) in neighboring regions is required for complete neural tube closure, consistent with results from other published models of neurulation (Clausi and Brodland, 1993;Brodland and Clausi, 1995).…”

Contraction and stress-dependent growth shape the forebrain of the early chicken embryo

“…Much is now known concerning the biophysical mechanisms that create the neural tube (Brodland and Clausi, 1995; Colas and Schoenwolf, 2001; Davidson and Keller, 1999) and those that drive cortical folding (Richman et al, 1975; Tallinen et al, 2016). However, processes that shape the brain between these two phases of neural development have received relatively little attention.…”

Do lamellipodia have the mechanical capacity to drive convergent extension?

“…While this hypothesized sequence of events may be true, its mechanical plausibility has not previously been investigated. Testing is crucial since the mechanics of cell-cell interactions and morphogenetic movements can be highly counterintuitive and the outcomes of mechanical interactions can be completely unexpected (Clausi and Brodland, 1993;Brodland and Clausi, 1995;Davidson et al, 1999;Brodland, 2004;Hardin and Walston, 2004). Indeed, "Without [such testing], we are only engaging in handwaving and wishful thinking about the performance of our models" (Gordon, 1985).…”