Limits...
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

Lissencephaly. Cortical malformations result from abnormal neuronal migration during the early stages of neurogenesis. The extensively thickened cortex typically only consists of four disorganized layers. Consistent with the clinical picture of lissencephaly (Budday et al., 2014a) (top right), the numerical simulation (Budday et al., 2014b) (bottom right) predicts the absence of folds for extensively thickened cortices.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4495345&req=5

Figure 6: Lissencephaly. Cortical malformations result from abnormal neuronal migration during the early stages of neurogenesis. The extensively thickened cortex typically only consists of four disorganized layers. Consistent with the clinical picture of lissencephaly (Budday et al., 2014a) (top right), the numerical simulation (Budday et al., 2014b) (bottom right) predicts the absence of folds for extensively thickened cortices.

Mentions: Figure 6 illustrates the abnormal neuronal migration during lissencephaly. Instead of forming six organized cortical layers as illustrated in Figure 1, the lissencephalic brain typically only forms four disorganized, thickened layers. Consistent with the pathology of lissencephaly (Budday et al., 2014a), the computational simulation of differential growth (Budday et al., 2014b) predicts that a considerably thickened cortex fails to fold since its growth-induced compressive stresses are too small to induce buckling.


Physical biology of human brain development.

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

Lissencephaly. Cortical malformations result from abnormal neuronal migration during the early stages of neurogenesis. The extensively thickened cortex typically only consists of four disorganized layers. Consistent with the clinical picture of lissencephaly (Budday et al., 2014a) (top right), the numerical simulation (Budday et al., 2014b) (bottom right) predicts the absence of folds for extensively thickened cortices.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 6: Lissencephaly. Cortical malformations result from abnormal neuronal migration during the early stages of neurogenesis. The extensively thickened cortex typically only consists of four disorganized layers. Consistent with the clinical picture of lissencephaly (Budday et al., 2014a) (top right), the numerical simulation (Budday et al., 2014b) (bottom right) predicts the absence of folds for extensively thickened cortices.
Mentions: Figure 6 illustrates the abnormal neuronal migration during lissencephaly. Instead of forming six organized cortical layers as illustrated in Figure 1, the lissencephalic brain typically only forms four disorganized, thickened layers. Consistent with the pathology of lissencephaly (Budday et al., 2014a), the computational simulation of differential growth (Budday et al., 2014b) predicts that a considerably thickened cortex fails to fold since its growth-induced compressive stresses are too small to induce buckling.

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