The stochastic search dynamics of interneuron migration.
Migration is a dynamic process in which a cell searches the environment and translates acquired information into somal advancement. In particular, interneuron migration during development is accomplished by two distinct processes: the extension of neurites tipped with growth cones; and nucleus translocation, termed nucleokinesis. The primary purpose of our study is to investigate neurite branching and nucleokinesis using high-resolution time-lapse confocal microscopy and computational modeling. We demonstrate that nucleokinesis is accurately modeled by a spring-dashpot system and that neurite branching is independent of the nucleokinesis event, and displays the dynamics of a stochastic birth-death process. This is in contrast to traditional biological descriptions, which suggest a closer relationship between the two migratory mechanisms. Our models are validated on independent data sets acquired using two different imaging protocols, and are shown to be robust to alterations in guidance cues and cellular migratory mechanisms, through treatment with brain-derived neurotrophic factor, neurotrophin-4, and blebbistatin. We postulate that the stochastic branch dynamics exhibited by interneurons undergoing guidance-directed migration permit efficient exploration of the environment.
Britto
Joanne M
JM
Howard Florey Institute, Florey Neuroscience Institutes, and Centre for Neuroscience, University of Melbourne, Melbourne, Australia.
Johnston
Leigh A
LA
Tan
Seong-Seng
SS
D000465:Algorithms; D000818:Animals; D001921:Brain / Q000254:growth & development / Q000502:physiology; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002465:Cell Movement; D003198:Computer Simulation; D016208:Databases, Factual; D049452:Green Fluorescent Proteins / Q000235:genetics; D006576:Heterocyclic Compounds, 4 or More Rings / Q000378:metabolism; D006801:Humans; D007395:Interneurons / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D018613:Microscopy, Confocal / Q000379:methods; D008959:Models, Neurological; D009414:Nerve Growth Factors / Q000378:metabolism; D016501:Neurites / Q000502:physiology; D013269:Stochastic Processes; D013997:Time Factors; D046509:Tissue Culture Techniques
D019208:Brain-Derived Neurotrophic Factor; D006576:Heterocyclic Compounds, 4 or More Rings; D009414:Nerve Growth Factors; D049452:Green Fluorescent Proteins; C472645:blebbistatin; C073922:neurotrophin 4