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Physical biology of human brain development.

Budday S, Steinmann P, Kuhl E - Front Cell Neurosci (2015)

Bottom Line: Neurodevelopment is a complex, dynamic process that involves a precisely orchestrated sequence of genetic, environmental, biochemical, and physical events.However, the precise impact of neuronal differentiation, migration, and connection on the physical forces during cortical folding remains unknown.We revisit cortical folding as the instability problem of constrained differential growth in a multi-layered system.

View Article: PubMed Central - PubMed

Affiliation: Chair of Applied Mechanics, Department of Mechanical Engineering, University of Erlangen/Nuremberg Erlangen, Germany.

ABSTRACT
Neurodevelopment is a complex, dynamic process that involves a precisely orchestrated sequence of genetic, environmental, biochemical, and physical events. Developmental biology and genetics have shaped our understanding of the molecular and cellular mechanisms during neurodevelopment. Recent studies suggest that physical forces play a central role in translating these cellular mechanisms into the complex surface morphology of the human brain. However, the precise impact of neuronal differentiation, migration, and connection on the physical forces during cortical folding remains unknown. Here we review the cellular mechanisms of neurodevelopment with a view toward surface morphogenesis, pattern selection, and evolution of shape. We revisit cortical folding as the instability problem of constrained differential growth in a multi-layered system. To identify the contributing factors of differential growth, we map out the timeline of neurodevelopment in humans and highlight the cellular events associated with extreme radial and tangential expansion. We demonstrate how computational modeling of differential growth can bridge the scales-from phenomena on the cellular level toward form and function on the organ level-to make quantitative, personalized predictions. Physics-based models can quantify cortical stresses, identify critical folding conditions, rationalize pattern selection, and predict gyral wavelengths and gyrification indices. We illustrate that physical forces can explain cortical malformations as emergent properties of developmental disorders. Combining biology and physics holds promise to advance our understanding of human brain development and enable early diagnostics of cortical malformations with the ultimate goal to improve treatment of neurodevelopmental disorders including epilepsy, autism spectrum disorders, and schizophrenia.

No MeSH data available.


Related in: MedlinePlus

Organization of a fully developed brain. In white matter, myelinated axons allow for rapid nerve impulse conduction; intermediate oligodendrocytes connect and form several myelin sheaths. Fibrous astrocytes ensure supply of nutrients and synaptic processing. In gray matter, neurons form synapses with each other and with protoplasmic astrocytes. In both white and gray matter, microglial cells contribute to clearance of debris and synapse remodeling.
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Figure 2: Organization of a fully developed brain. In white matter, myelinated axons allow for rapid nerve impulse conduction; intermediate oligodendrocytes connect and form several myelin sheaths. Fibrous astrocytes ensure supply of nutrients and synaptic processing. In gray matter, neurons form synapses with each other and with protoplasmic astrocytes. In both white and gray matter, microglial cells contribute to clearance of debris and synapse remodeling.

Mentions: Figure 2 sketches the final organization of the brain, once all components have fully developed and connected. Besides cell division and cell migration, the formation of connections is a major factor of normal brain development. Before midgestation, there is essentially no direct connection between the cortex and the rest of the central nervous system. At this point, there are only indirect connections between cortical and subcortical structures and the subplate (Haynes et al., 2005). As connectivity develops, axons form and multiply their branches. During the second half of gestation, axons extend branches to numerous cortical and subcortical targets, until each neuron connects with thousands of other neurons (Raybaud et al., 2013). The mechanical forces during this phase of axonal elongation have been extensively studied (Suter and Miller, 2011; O'Toole et al., 2015). They have lead to the popular but controversial hypothesis of surface morphogenesis through axonal tension and compact wiring (Mitchison, 1991). Axonal tension, a mechanisms to bring functionally related units topographically closer together (VanEssen, 1997), can explain folding with realistic stiffness ratios, but disagrees with dissection experiments (Xu et al., 2010). Differential growth, a mechanism to release residual stresses by surface buckling (Ronan et al., 2014), agrees with dissection experiments, but requires unrealistic stiffness ratios (Richman et al., 1975). Combining both mechanisms has motivated theories of stretch- and stress-driven growth, concepts that agree with both realistic stiffness ratios and maximum principal stress distributions (Bayly et al., 2013; Budday et al., 2014b).


Physical biology of human brain development.

Budday S, Steinmann P, Kuhl E - Front Cell Neurosci (2015)

Organization of a fully developed brain. In white matter, myelinated axons allow for rapid nerve impulse conduction; intermediate oligodendrocytes connect and form several myelin sheaths. Fibrous astrocytes ensure supply of nutrients and synaptic processing. In gray matter, neurons form synapses with each other and with protoplasmic astrocytes. In both white and gray matter, microglial cells contribute to clearance of debris and synapse remodeling.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4495345&req=5

Figure 2: Organization of a fully developed brain. In white matter, myelinated axons allow for rapid nerve impulse conduction; intermediate oligodendrocytes connect and form several myelin sheaths. Fibrous astrocytes ensure supply of nutrients and synaptic processing. In gray matter, neurons form synapses with each other and with protoplasmic astrocytes. In both white and gray matter, microglial cells contribute to clearance of debris and synapse remodeling.
Mentions: Figure 2 sketches the final organization of the brain, once all components have fully developed and connected. Besides cell division and cell migration, the formation of connections is a major factor of normal brain development. Before midgestation, there is essentially no direct connection between the cortex and the rest of the central nervous system. At this point, there are only indirect connections between cortical and subcortical structures and the subplate (Haynes et al., 2005). As connectivity develops, axons form and multiply their branches. During the second half of gestation, axons extend branches to numerous cortical and subcortical targets, until each neuron connects with thousands of other neurons (Raybaud et al., 2013). The mechanical forces during this phase of axonal elongation have been extensively studied (Suter and Miller, 2011; O'Toole et al., 2015). They have lead to the popular but controversial hypothesis of surface morphogenesis through axonal tension and compact wiring (Mitchison, 1991). Axonal tension, a mechanisms to bring functionally related units topographically closer together (VanEssen, 1997), can explain folding with realistic stiffness ratios, but disagrees with dissection experiments (Xu et al., 2010). Differential growth, a mechanism to release residual stresses by surface buckling (Ronan et al., 2014), agrees with dissection experiments, but requires unrealistic stiffness ratios (Richman et al., 1975). Combining both mechanisms has motivated theories of stretch- and stress-driven growth, concepts that agree with both realistic stiffness ratios and maximum principal stress distributions (Bayly et al., 2013; Budday et al., 2014b).

Bottom Line: Neurodevelopment is a complex, dynamic process that involves a precisely orchestrated sequence of genetic, environmental, biochemical, and physical events.However, the precise impact of neuronal differentiation, migration, and connection on the physical forces during cortical folding remains unknown.We revisit cortical folding as the instability problem of constrained differential growth in a multi-layered system.

View Article: PubMed Central - PubMed

Affiliation: Chair of Applied Mechanics, Department of Mechanical Engineering, University of Erlangen/Nuremberg Erlangen, Germany.

ABSTRACT
Neurodevelopment is a complex, dynamic process that involves a precisely orchestrated sequence of genetic, environmental, biochemical, and physical events. Developmental biology and genetics have shaped our understanding of the molecular and cellular mechanisms during neurodevelopment. Recent studies suggest that physical forces play a central role in translating these cellular mechanisms into the complex surface morphology of the human brain. However, the precise impact of neuronal differentiation, migration, and connection on the physical forces during cortical folding remains unknown. Here we review the cellular mechanisms of neurodevelopment with a view toward surface morphogenesis, pattern selection, and evolution of shape. We revisit cortical folding as the instability problem of constrained differential growth in a multi-layered system. To identify the contributing factors of differential growth, we map out the timeline of neurodevelopment in humans and highlight the cellular events associated with extreme radial and tangential expansion. We demonstrate how computational modeling of differential growth can bridge the scales-from phenomena on the cellular level toward form and function on the organ level-to make quantitative, personalized predictions. Physics-based models can quantify cortical stresses, identify critical folding conditions, rationalize pattern selection, and predict gyral wavelengths and gyrification indices. We illustrate that physical forces can explain cortical malformations as emergent properties of developmental disorders. Combining biology and physics holds promise to advance our understanding of human brain development and enable early diagnostics of cortical malformations with the ultimate goal to improve treatment of neurodevelopmental disorders including epilepsy, autism spectrum disorders, and schizophrenia.

No MeSH data available.


Related in: MedlinePlus