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

Abstract

During early vertebrate development, local constrictions, or sulci, form to divide the forebrain into the diencephalon, telencephalon, and optic vesicles. These partitions are maintained and exaggerated as the brain tube inflates, grows, and bends. Combining quantitative experiments on chick embryos with computational modeling, we investigated the biophysical mechanisms that drive these changes in brain shape. Chemical perturbations of contractility indicated that actomyosin contraction plays a major role in the creation of initial constrictions (Hamburger-Hamilton stages HH11–12), and fluorescent staining revealed that F-actin is circumferentially aligned at all constrictions. A finite element model based on these findings shows that the observed shape changes are consistent with circumferential contraction in these regions. To explain why sulci continue to deepen as the forebrain expands (HH12–20), we speculate that growth depends on wall stress. This idea was examined by including stress-dependent growth in a model with cerebrospinal fluid pressure and bending (cephalic flexure). The results given by the model agree with observed morphological changes that occur in the brain tube under normal and reduced eCSF pressure, quantitative measurements of relative sulcal depth versus time, and previously published patterns of cell proliferation. Taken together, our results support a biphasic mechanism for forebrain morphogenesis consisting of differential contractility (early) and stress-dependent growth (late).

Molecular and mechanical signals determine morphogenesis of the cerebral hemispheres in the chicken embryo

“…As a fraction of total DMB expansion, the contribution of elastic stretch (approximately 10%) was considerably smaller than the contribution of growth (50-100%), in agreement with studies at earlier stages (Garcia et al, 2017). Importantly, our results indicate that circumferential growth depends on eCSF pressure but radial growth does not (Fig.…”

“…After neurulation, local constrictions along the length (rostralcaudal axis) of the neural tube produce distinct primary brain vesicles: the forebrain, midbrain and hindbrain (Filas et al, 2012;Garcia et al, 2017). As described extensively by Puelles et al (2012), the forebrain can be further segmented along its length into the secondary prosencephalon (SP, rostral tip) and diencephalon (between the SP and midbrain) ( Fig.…”

“…1A). Once the neural tube seals, embryonic cerebrospinal fluid (eCSF) is secreted into the lumen of the brain, and all vesicles undergo dramatic, pressuredriven expansion (Lowery and Sive, 2009;Garcia et al, 2017) (Fig. 1B).…”

Mechanics of cortical folding: stress, growth and stability

“…An additional, intriguing, possibility is that mechanical stress itself may initiate patterns of proliferation, differentiation, migration and maturation. Studies in chicken embryos suggest that neuroepithelial progenitor cells, precursors to basal radial glial cells in the oSVZ, proliferate in response to mechanical feedback [13,15,16]. Substrate mechanical properties [63] and mechanical tension [64] have been shown to affect the differentiation of stem cells into neurons.…”

How the embryonic chick brain twists

“…Results from these studies suggest that the SPL plays a mechanical role in facilitating cardiac torsion that may be similar to the role of the VM in inducing brain torsion reported here. A more recent study implies that both differential contractility and stress-dependent growth play key roles in early brain morphogenesis [42].…”