Chiral Neuronal Motility: The Missing Link between Molecular Chirality and Brain Asymmetry

Abstract

Left–right brain asymmetry is a fundamental property observed across phyla from invertebrates to humans, but the mechanisms underlying its formation are still largely unknown. Rapid progress in our knowledge of the formation of body asymmetry suggests that brain asymmetry might be controlled by the same mechanisms. However, most of the functional brain laterality, including language processing and handedness, does not share common mechanisms with visceral asymmetry. Accumulating evidence indicates that asymmetry is manifested as chirality at the single cellular level. In neurons, the growth cone filopodia at the tips of neurites exhibit a myosin V-dependent, left-helical, and right-screw rotation, which drives the clockwise circular growth of neurites on adhesive substrates. Here, I propose an alternative model for the formation of brain asymmetry that is based on chiral neuronal motility. According to this chiral neuron model, the molecular chirality of actin filaments and myosin motors is converted into chiral neuronal motility, which is in turn transformed into the left–right asymmetry of neural circuits and lateralized brain functions. I also introduce automated, numerical, and quantitative methods to analyze the chirality and the left–right asymmetry that would enable the efficient testing of the model and to accelerate future investigations in this field.

Keywords

• left–right asymmetry
• brain lateralization
• cell chirality
• growth cone filopodia
• neurite growth
• actin filaments
• myosin V
• Riesz transform-differential interference contrast microscopy
• structure tensor
• optical flow