BME Seminar Series - Raymond Keller, University of Virginia
Friday,
March 29, 2019
11:00 AM - 12:00 PM
Title:
Engineering Morphogenesis: The Specificity of Gastrulation and Body Plan Formation Result from Mechanical Interactions
Abstract:
The early morphogenesis (gastrulation and shaping of the body plan) of the frog (Xenopus laevis) occurs by the physiological and mechanical integration of the force-generating activities of about 12-16 thousand cells, acting within a 1.2 mm diameter spherical embryo. Although the process as a whole seems intimidatingly complex, it is fundamentally a biomechanical process, and its analysis is made simpler by approaching it as such. I will describe several region-specific morphogenic domains that comprise the Xenopus embryo, each with a characteristic force-generating cellular behavior. These behaviors include actomyosin-driven cell shape change, polarized cell adhesion, protrusive activity and traction, and changes in tissue surface tension. The specific properties of each morphogenic domain depends on the details of its characteristic cell behavior but also on its intercellular mechanical linkages and the timing, geometry and rate of its progression. In turn, these regionally-generated, domain-level forces are mechanically integrated over the entire embryo in a context-dependent manner, and again, the emerging specificity of the result at the whole embryo scale is dependent on their geometry, timing, and mechanical linkages. Finally, these active, force-generating processes produce strain in mechanically linked, passively deformed tissues. Our collaborators have shown that this strain regulates polarity and other differentiating properties of cells in these tissues, suggesting that strain-dependant mechano-transduction may be an important large scale embryonic organizer. Other, classic evidence suggests that these force-generating processes themselves may be initiated and regulated in an ongoing manner by strain. For emerging themes: 1) specificity of morphogenesis results from mechanical integration at each successive level; 2) specificity of output is context dependent; 3) different force-generating cellular processes can generate similar morphogenic events in different species or in different situations in the same species; 4) mapping function of gene products on to the biophysical parameter space has resulted in evolution of many different, highly effective, and interesting morphogenic machines. As embryologists, we have only scratched the surface of this problem, and application of more sophisticated engineering principles and approaches will greatly enhance our understanding of morphogenesis in development and disease.
Engineering Morphogenesis: The Specificity of Gastrulation and Body Plan Formation Result from Mechanical Interactions
Abstract:
The early morphogenesis (gastrulation and shaping of the body plan) of the frog (Xenopus laevis) occurs by the physiological and mechanical integration of the force-generating activities of about 12-16 thousand cells, acting within a 1.2 mm diameter spherical embryo. Although the process as a whole seems intimidatingly complex, it is fundamentally a biomechanical process, and its analysis is made simpler by approaching it as such. I will describe several region-specific morphogenic domains that comprise the Xenopus embryo, each with a characteristic force-generating cellular behavior. These behaviors include actomyosin-driven cell shape change, polarized cell adhesion, protrusive activity and traction, and changes in tissue surface tension. The specific properties of each morphogenic domain depends on the details of its characteristic cell behavior but also on its intercellular mechanical linkages and the timing, geometry and rate of its progression. In turn, these regionally-generated, domain-level forces are mechanically integrated over the entire embryo in a context-dependent manner, and again, the emerging specificity of the result at the whole embryo scale is dependent on their geometry, timing, and mechanical linkages. Finally, these active, force-generating processes produce strain in mechanically linked, passively deformed tissues. Our collaborators have shown that this strain regulates polarity and other differentiating properties of cells in these tissues, suggesting that strain-dependant mechano-transduction may be an important large scale embryonic organizer. Other, classic evidence suggests that these force-generating processes themselves may be initiated and regulated in an ongoing manner by strain. For emerging themes: 1) specificity of morphogenesis results from mechanical integration at each successive level; 2) specificity of output is context dependent; 3) different force-generating cellular processes can generate similar morphogenic events in different species or in different situations in the same species; 4) mapping function of gene products on to the biophysical parameter space has resulted in evolution of many different, highly effective, and interesting morphogenic machines. As embryologists, we have only scratched the surface of this problem, and application of more sophisticated engineering principles and approaches will greatly enhance our understanding of morphogenesis in development and disease.
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