Project 1: Unveiling the Biomechanical Principles of Early Embryonic Heart and Brain Morphogenesis The long-term goal is to unveil the critical regulatory roles of mechanical forces in embryonic morphogenesis from subcellular to tissue and organism levels. The objective of this project is to identify the biomechanical mechanisms that drive the shape changes in early heart and brain development using chick embryos as a model system. The overarching hypothesis is that, besides gene regulation, the growth and morphogenesis of the brain are regulated by spatial-temporally distributed mechanical stresses and mechanical feedback control mechanisms. This project will focus on the following aims to address the role of mechanical forces in in early brain morphogenesis: 1) determine the biomechanical mechanisms that drive torsion (twisting) and flexture (bending) of the early heart; 2) identify the biomechanical mechanisms that drive torsion (twisting) and flexture (bending) of the early brain; 3) identify the mechanical feedback control and regulation mechanism in morphogenesis; 4) examine the roles of body forces, such as gravity and buoyancy, in morphogenesis. Significance and Innovations Creation and looping of the heart tube are vitally important processes during embryonic development. Looping abnormalities likely underlie some of the cardiac malformations that occur in as many as 1% of liveborn and 10% of stillborn human births, and such defects may result in numerous spontaneous abortions during the first trimester. Moreover, available evidence suggests that looping directionality is rooted in events that occur before looping begins. While rapid progress is being made in defining the genetic perturbations behind abnormal cardiac morphogenesis, the mechanisms of gene action remain poorly understood. To fully understand the causes of developmental abnormalities in the heart, it is important to determine the fundamental biomechanical principles that govern cardiac morphogenesis. Combining experimental and state-of-the-art computational models, this project will address some crucial questions about how mechanical forces are integrated and regulated to create the looped heart tube. Meanwhile, many congenital brain defects are rooted in early morphogenesis. For example, abnormalities in brain ventricle size (potentially due to aberrant pressure loading) and shape have been implicated in a wide variety of neurological disorders, including schizophrenia, autism, hydrocephalus, and mental retardation. Understanding early morphogenesis in response to altered loads also has important implications in the fields of microsurgery, regenerative medicine, and tissue engineering. Determining how neuroepithelial cells respond to mechanical perturbations could provide important predictive information for tissue engineering. Moreover, the brain torsion (or axial rotation) is one of the earliest organ-level left-right (L-R) asymmetry event in development. It is known that birth defects can result when the process of L–R specification is perturbed, including situs inversus (inversion of the positions of visceral organs), isomerism (mirror image symmetry of bilaterally asymmetric tissues), and heterotaxia (random and independent occurrence of laterality). Ultimately, researchers searching for the link between gene expression and morphogenesis. The biomechanical principles can we hope that this work will aid also be applied to develop bioinspired and biohybrid soft robotics.
Project 1: Unveiling the Biomechanical Principles of Early Embryonic Heart and Brain Morphogenesis The long-term goal is to unveil the critical regulatory roles of mechanical forces in embryonic morphogenesis from subcellular to tissue and organism levels. The objective of this project is to identify the biomechanical mechanisms that drive the shape changes in early heart and brain development using chick embryos as a model system. The overarching hypothesis is that, besides gene regulation, the growth and morphogenesis of the brain are regulated by spatial-temporally distributed mechanical stresses and mechanical feedback control mechanisms. This project will focus on the following aims to address the role of mechanical forces in in early brain morphogenesis: 1) determine the biomechanical mechanisms that drive torsion (twisting) and flexture (bending) of the early heart; 2) identify the biomechanical mechanisms that drive torsion (twisting) and flexture (bending) of the early brain; 3) identify the mechanical feedback control and regulation mechanism in morphogenesis; 4) examine the roles of body forces, such as gravity and buoyancy, in morphogenesis. Significance and Innovations Creation and looping of the heart tube are vitally important processes during embryonic development. Looping abnormalities likely underlie some of the cardiac malformations that occur in as many as 1% of liveborn and 10% of stillborn human births, and such defects may result in numerous spontaneous abortions during the first trimester. Moreover, available evidence suggests that looping directionality is rooted in events that occur before looping begins. While rapid progress is being made in defining the genetic perturbations behind abnormal cardiac morphogenesis, the mechanisms of gene action remain poorly understood. To fully understand the causes of developmental abnormalities in the heart, it is important to determine the fundamental biomechanical principles that govern cardiac morphogenesis. Combining experimental and state-of-the-art computational models, this project will address some crucial questions about how mechanical forces are integrated and regulated to create the looped heart tube. Meanwhile, many congenital brain defects are rooted in early morphogenesis. For example, abnormalities in brain ventricle size (potentially due to aberrant pressure loading) and shape have been implicated in a wide variety of neurological disorders, including schizophrenia, autism, hydrocephalus, and mental retardation. Understanding early morphogenesis in response to altered loads also has important implications in the fields of microsurgery, regenerative medicine, and tissue engineering. Determining how neuroepithelial cells respond to mechanical perturbations could provide important predictive information for tissue engineering. Moreover, the brain torsion (or axial rotation) is one of the earliest organ-level left-right (L-R) asymmetry event in development. It is known that birth defects can result when the process of L–R specification is perturbed, including situs inversus (inversion of the positions of visceral organs), isomerism (mirror image symmetry of bilaterally asymmetric tissues), and heterotaxia (random and independent occurrence of laterality). Ultimately, researchers searching for the link between gene expression and morphogenesis. The biomechanical principles can we hope that this work will aid also be applied to develop bioinspired and biohybrid soft robotics.