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Supported by: National Institute of Child Health and Human Development |
Biomechanics of Morphogenesis How does the form of the embryo take shape from a simple mass of cells? Morphogenesis is one of the great mysteries of modern biology. Timelapse movies of embryos show a wide variety of orchestrated cell shape changes and cell migrations. In addition to the molecular regulators of morphogenesis, controlling cell motility and pattern formation, we must also consider morphogenesis as an intrinsically mechanical process. Tissues change shape (deform) and move over one another (shear). Some cells pull and exert traction (stress) while others passively change shape (strain) in response to forces generated elsewhere. Patterns of active cell processes and the passive response of tissues to them are programmed in a complex manner through spatially and temporally controled gene expression, post-translational modifications of their protein products, and interactions with the cellular environment. A biomechanical approach is an integrated approach to studying morphogenesis at a variety of scales from molecular-genetic scales through the cell-level, tissue-level, and finally to an understanding of how the embryo itself is constructed.
Convergence and Extension Prospective dorsal tissues of the early embryo form as cells move from an "equatorial" belt, centered on the anterior midline, into a linear array, centered on the dorsal midline. Through coordinated movements and cell rearrangements cells from prospective mesoderm, neural, and endodermal tissues first move toward the midline of the blastopore lip. Prospective mesoderm and endoderm cells move over the blastopore lip as well as over an inner "lip" at the base of the cleft of Brachet and join the dorsal array of tissue. Multiple processes are responsible for driving these early movements such as epiboly, radial intercalation, vegetal rotation, and mediolateral cell intercalation. Once the three basic germ layers (ectoderm, mesoderm, and endoderm) of the dorsal axis are assembled these tissues engage a strong phase of axis elongation driven primarily by mediolateral cell intercalation in the process known as convergence and extension.
Mesendoderm Migration A ring of cells within the embryo are specified to moves many hundreds of microns and form both mesoderm and endoderm, thus mes---endoderm, within the "belly" of the embryo. In the early frog embryo these cells begin their migration as a ring/mass of mesenchymal cells that lie more vegetal and deeper than the axial and paraxial mesoderm. They migrate together from all 360 degrees of the marginal zone and the leading cells converge to a point under the animal cap ectoderm enclosing the blastocoel from within the embryo. Mesendoderm cells eventually form ventral body wall and organ structures such as blood, endothelial vessels and the peritoneum. How do cell-cell and cell-substrate interactions modulate the dramatic cell migration that carries these "ventral" tissues hundreds of microns in less than 4 hours?
Neural Tube Closure The central nervous system is almost entirely derived from cells that originate on the surface of the embryo. In the frog Xenopus laevis a mix of tissue rolling and cell migration move these cells over 6 hours into the embryo where they differentiate into neural crest, neurons, and spinal cord. What are the mechanical and cell-biological events driving neural fold formation and neural tube closure?
Wound Healing If an embryo is wounded or pricked the cells within and surrounding the wound participate in an extremely rapid series of movements that draw the wound closed. Cell shape changes and cell migration bring about wound closure in less than 60 minutes. Wounds can be made in a controlled manner in a tissue that is expressing mutant proteins. What are the relevant molecular components of a "cellular" tissue that mediate these events?
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