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 brodland collage

Mechanics of Neurulation

During early embryo development, sheets of tissue called epithelia must undergo specific patterns of motion in order to form organs and other critical structures (Movie 1). Sometimes, for reasons not totally understood, irregularities occur in these motions and a birth defect - such as spina bifida, cleft lip or a cardiac septum defect - arises. The goal of this work is to use computational modeling and experiments to better understand why these defects arise and, hopefully, to devise improved prevention strategies.


Movie 1 - Neurulation in an amphibian (Ambystoma mexicanum) embryo. During this process, the neural plate rolls up to form a sealed tube. This tube is the precursor of the spinal cord and brain. If even a small section of the tube does not close, a birth defect such as spina bifida can result.

Movie 2 - A multi-scale computational model of neurulation corresponding to part of the process shown in Movie 1, above.

Our multi-scale computational models bridge the cellular-tissue-whole embryo length scales [1-4]. And our experiments [5-7] provide data for model validation at each of each of these scales. Adjustments can be made to the model to investigate how irregularities in gene expression or the mechanical properties of specific tissues might affect tissue motions and their outcomes.

References


1. Brodland, G.W., Chen, D.I.-L., and Veldhuis, J.H., 2006, "A Cell-based Constitutive Model for Embryonic Epithelia and Other Planar Aggregates of Biological Cells," International Journal of Plasticity, Vol. 22, pp. 965-995. 10.1016/j.ijplas.2005.05.002.

2. Brodland, G.W., Viens, D. and Veldhuis, J.H., 2007, "A New Cell-based FE Model for the Mechanics of Embryonic Epithelia," Computer Methods in Biomechanics and Biomedical Engineering, Vol 10 (2), pp. 121-128. doi: 10.1080/10255840601124704.

3. Chen, X. and Brodland G.W., 2008, "Multi-scale Finite Element Modeling Allows the Mechanics of Amphibian Neurulation to be Elucidated," Physical Biology, Vol. 5 (1), pp. 1-15. doi: 10.1088/1478-3975/5/1/015003.

4. Brodland, G.W., Chen, X., Lee, P. and Marsden, M., 2010, "From genes to neural tube defects (NTDs): Insights from multiscale computational modeling," HFSP Journal, Vol. 4, pp. 142-152. doi: 10.2976/1.3338713.

5. Wiebe, C.J. and Brodland, G.W., 2005, "Tensile Properties of Embryonic Epithelia Measured Using a Novel Instrument," Journal of Biomechanics, Vol. 38, pp. 2087-2094. doi: 10.1016/j.jbiomech.2004.09.005.

6. Benko, R. and Brodland, G.W., 2007, "Measurement of in vivo Stress resultants in Neurulation-stage Amphibian Embryos," Annals of Biomedical Engineering, Vol. 35 (4) pp 672-681.10.1007/s10439-006-9250-1.

7. Brodland, G.W., Yang, J and Sweny, J, 2009, "Cellular interfacial and surface tensions determined from aggregate compression tests using a finite element model," HFSP Journal, Vol. 3, pp. 273-281. doi: 10.2976/1.3175812.