Positions are available for highly qualified and motivated candidates to study the physical principles of morphogenesis in the Davidson Laboratory at the University of Pittsburgh in the Department of Bioengineering. The laboratory focuses on studying the molecular-, cellular, and tissue-scale processes that regulate mechanical properties and force-production during morphogenesis. Projects involve a combination of biophysics, cell biology, bioengineering, and embryology.
Abstract: The formation of the neural tube is crucial for the proper development of the brain and spinal cord and its failure results in congenital disorder known as neural tube defects (NTDs). NTDs are estimated to affect 100,000 births world wide each year. Several known genetic mutations are associated with NTDs but the physical mechanisms by which they act or their effects on neural tube morphogenesis remain unclear. The neural tube begins as a flat sheet of epithelial cells on the surface of the embryo called the neural plate that undergoes a series of shape changes that turn it into an elongated tubular structure, internalized within the embryo. These coordinated tissue level deformations are orchestrated by integrated behaviors of cells within the embryo. Our study aimed to identify the cell behaviors accompanying neural plate shaping, the first step of neural tube formation, in the aquatic frog, Xenopus laevis, embryo.
Deepthi has joined McKinsey & Company | Global management consulting.
Abstract: Embryonic development involves large scale tissue movements that construct complex three dimensional tissue structures, governed by basic physical principles. Fine-grained control of mechanical properties and force production is critical to the successful placement of tissues and organs within the embryo. The active forces and passive mechanical properties not only physically construct the tissue structures, but may also provide feedback to remodel cells, their extracellular matrix, and intercellular adhesions. …
“Mechanics of Morphogenesis” funded through NIH! See the News.
“The goal of this proposal is to understand the physical mechanisms that drive cell shape changes, control cell behaviors, generate forces, and establish passive tissue properties such as stiffness, active force production by convergence and extension, and how passive mechanics and active forces shape a vertebrate embryo. The significance of our work extends beyond defining the mechanical conditions and their role in early development to provide fundamental physical principles for future tissue engineers, allow a more complete understanding of the contribution of tissue mechanics to birth defects, and to understand the role of tissue mechanics in oncogenesis.”
Newly Published: T. R. Jackson, H. Y. Kim, U. L. Balakrishnan, C. Stuckenholz, and L. A. Davidson (2017). Spatiotemporally controlled mechanical cues drive progenitor mesenchymal-to-epithelial transition enabling proper heart formation and function. Current Biology. 27: 1326–1335.
Describes a mesenchymal-to-epithelial transition (MET) in heart progenitor cells that is regulated by temporally specific mechanical cues originating from the endoderm. Accelerating or delaying MET by manipulating the mechanical microenvironment of the heart-forming region leads to abnormal heart anatomy
Newly Published: Chanet, S., Miller, C. J., Vaishnav, E. D., Ermentrout, B., Davidson, L. A. and Martin, A. C. (2017). Actomyosin meshwork mechanosensing enables tissue shape to orient cell force. Nature Communications 8. https://dx.doi.org/10.1038%2Fncomms15014
“Sculpting organism shape requires that cells produce forces with proper directionality. Thus, it is critical to understand how cells orient the cytoskeleton to produce forces that deform tissues.”
‘Embryology and morphology cannot proceed independently of all reference to the general laws of matter, to the laws of physics and of mechanics’.
—W. His in a letter to Professor Sir William Turner (1888) On the principles of animal morphology. Proc. R. Soc. Edinb. 15, 287–298.
Abstract: In early heart development, bilateral fields of heart progenitor cells (HPCs) undergo a large-scale movement from the anterior lateral plate mesoderm to merge on the ventral midline, undergoing a mesenchymal-to-epithelial transition (MET) halfway through this process. While the heart is the first functioning organs in the developing embryo, a comprehensive model for early heart development that integrates both physical mechanisms and molecular signaling pathways remains elusive. Here, we utilize Xenopus embryos to investigate the role of mechanical cues in driving MET in HPCs and show how dysregulation of these cues can cause congenital heart defects (CHDs). From this integrated analysis of HPC polarity and mechanics, we propose that normal heart development requires HPCs to undergo a critical behavioral and phenotypic transition on their way to the ventral midline and that this transition is driven in response to the changing mechanical properties of their endoderm substrate. We conclude that the etiology underlying many CHDs may involve errors in mechanical signaling and MET.
Tim can be found in his new position in R&D at Essen Biosciences (now Sartorius).
Newly Published: Stooke‐Vaughan, G., Davidson, L. and Woolner, S. (2017). Xenopus as a model for studies in mechanical stress and cell division. Genesis. – “We exist in a physical world, and cells within biological tissues must respond appropriately to both environmental forces and forces generated within the tissue to ensure normal development and homeostasis. …”