title: 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).
authors.affiliation: Department of Biomedical Engineering, Washington University, 1 Brookings Drive, Saint Louis, MO 63130, USA. Electronic address: karaellspermann@wustl.edu.
authors.forename: Kara E
authors.initials: KE
authors.lastname: Garcia
authors.affiliation: Department of Mechanical Engineering and Material Science, Washington University, 1 Brookings Drive, Saint Louis, MO 63130, USA.
authors.forename: Ruth J
authors.initials: RJ
authors.lastname: Okamoto
authors.affiliation: Department of Biomedical Engineering, Washington University, 1 Brookings Drive, Saint Louis, MO 63130, USA; Department of Mechanical Engineering and Material Science, Washington University, 1 Brookings Drive, Saint Louis, MO 63130, USA.
authors.forename: Philip V
authors.initials: PV
authors.lastname: Bayly
authors.affiliation: Department of Biomedical Engineering, Washington University, 1 Brookings Drive, Saint Louis, MO 63130, USA; Department of Mechanical Engineering and Material Science, Washington University, 1 Brookings Drive, Saint Louis, MO 63130, USA.
authors.forename: Larry A
authors.initials: LA
authors.lastname: Taber
mesh_terms: D000199:Actins / Q000502:physiology*; D000818:Animals; D049109:Cell Proliferation; D002642:Chick Embryo; D003198:Computer Simulation; D016548:Prosencephalon / Q000254:growth & development*
chemical_list: D000199:Actins
keywords: Actomyosin; Brain; Cerebrospinal fluid; Development; Mechanical feedback; Morphogenesis