In human embryos, the primary subdivisions of the brain (forebrain, midbrain, and hindbrain) are formed by the fourth week of gestation. During this time, the primitive eyes (optic vesicles) emerge as protrusions from the forebrain. The forms of these organs are highly conserved. Abnormalities in size and shape of the early brain are known to cause serious neurological disorders such as anencephaly, hydrocephalus, autism, and schizophrenia, while improper eye morphogenesis can cause coloboma and microphthalmia, leading to severe visual impairment. Prevention and treatment of these maladies requires understanding of their root cause. While much is now known about the molecular and genetic factors that regulate brain and eye development, the mechanical processes that actually create these structures remain poorly understood. The main objective of this proposed research is to determine the morphogenetic mechanisms that shape the early embryonic brain and eye.
The specific aims are the following: (1) Determine the mechanisms that drive growth and morphogenesis of the developing brain vesicles. (2) Determine the mechanisms that drive growth and morphogenesis of the optic vesicle before the optic cup forms. (3) Determine the mechanisms that drive invagination and shaping of the optic cup. To accomplish these aims, we will integrate computational modeling with quantitative experimental measurements. The models are based on fundamental engineering theories of nonlinear solid mechanics. The experiments, to be conducted on chick and mouse embryos, will employ high-resolution optical coherence tomography (OCT) and fluorescence imaging to measure changes in global and local geometry (e.g., curvature and wall strains) and microstructure (e.g., actin distribution), microdissection to determine and perturb tissue stress, drug exposure and genetic knockouts to perturb cellular function, and measurements of embryonic cerebrospinal fluid pressure and regional mechanical properties. This project will provide important new insights into the morphogenetic mechanisms of brain and eye development.
Abnormalities in size and shape of the early brain are known to cause serious neurological disorders such as anencephaly, hydrocephalus, autism, and schizophrenia, while improper eye development can cause visual impairment. Prevention and treatment of these maladies requires understanding their root cause. This project will provide important new understanding of the morphogenetic mechanisms that create the embryonic brain and eye.
| Oltean, Alina; Taber, Larry A (2018) Apoptosis generates mechanical forces that close the lens vesicle in the chick embryo. Phys Biol 15:025001 |
| Espinosa, M Gabriela; Taber, Larry A; Wagenseil, Jessica E (2018) Reduced embryonic blood flow impacts extracellular matrix deposition in the maturing aorta. Dev Dyn 247:914-923 |
| Garcia, Kara E; Robinson, Emma C; Alexopoulos, Dimitrios et al. (2018) Dynamic patterns of cortical expansion during folding of the preterm human brain. Proc Natl Acad Sci U S A 115:3156-3161 |
| Hosseini, Hadi S; Taber, Larry A (2018) How mechanical forces shape the developing eye. Prog Biophys Mol Biol 137:25-36 |
| Kroenke, Christopher D; Bayly, Philip V (2018) How Forces Fold the Cerebral Cortex. J Neurosci 38:767-775 |
| Hosseini, Hadi S; Garcia, Kara E; Taber, Larry A (2017) A new hypothesis for foregut and heart tube formation based on differential growth and actomyosin contraction. Development 144:2381-2391 |
| Garcia, Kara E; Okamoto, Ruth J; Bayly, Philip V et al. (2017) Contraction and stress-dependent growth shape the forebrain of the early chicken embryo. J Mech Behav Biomed Mater 65:383-397 |
| Chen, Zi; Guo, Qiaohang; Dai, Eric et al. (2016) How the embryonic chick brain twists. J R Soc Interface 13: |
| Oltean, Alina; Huang, Jie; Beebe, David C et al. (2016) Tissue growth constrained by extracellular matrix drives invagination during optic cup morphogenesis. Biomech Model Mechanobiol 15:1405-1421 |
| Shi, Yunfei; Varner, Victor D; Taber, Larry A (2015) Why is cytoskeletal contraction required for cardiac fusion before but not after looping begins? Phys Biol 12:016012 |
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