title: Self-organizing circuit assembly through spatiotemporally coordinated neuronal migration within geometric constraints.
abstract: BACKGROUND
  Neurons are dynamically coupled with each other through neurite-mediated adhesion during development. Understanding the collective behavior of neurons in circuits is important for understanding neural development. While a number of genetic and activity-dependent factors regulating neuronal migration have been discovered on single cell level, systematic study of collective neuronal migration has been lacking. Various biological systems are shown to be self-organized, and it is not known if neural circuit assembly is self-organized. Besides, many of the molecular factors take effect through spatial patterns, and coupled biological systems exhibit emergent property in response to geometric constraints. How geometric constraints of the patterns regulate neuronal migration and circuit assembly of neurons within the patterns remains unexplored.
  
  
  RESULTS
  We established a two-dimensional model for studying collective neuronal migration of a circuit, with hippocampal neurons from embryonic rats on Matrigel-coated self-assembled monolayers (SAMs). When the neural circuit is subject to geometric constraints of a critical scale, we found that the collective behavior of neuronal migration is spatiotemporally coordinated. Neuronal somata that are evenly distributed upon adhesion tend to aggregate at the geometric center of the circuit, forming mono-clusters. Clustering formation is geometry-dependent, within a critical scale from 200 µm to approximately 500 µm. Finally, somata clustering is neuron-type specific, and glutamatergic and GABAergic neurons tend to aggregate homo-philically.
  
  
  CONCLUSIONS
  We demonstrate self-organization of neural circuits in response to geometric constraints through spatiotemporally coordinated neuronal migration, possibly via mechanical coupling. We found that such collective neuronal migration leads to somata clustering, and mono-cluster appears when the geometric constraints fall within a critical scale. The discovery of geometry-dependent collective neuronal migration and the formation of somata clustering in vitro shed light on neural development in vivo.
authors: Chinese Academy of Sciences Key Lab for Biological Effects of Nanomaterials and Nanosafety, National Center for NanoScience and Technology, Beijing, China.
authors: Yi
authors: Y
authors: Sun
authors: Zhuo
authors: Z
authors: Huang
authors: Kaixuan
authors: K
authors: Yang
authors: Wenwen
authors: W
authors: Liu
authors: Yunyan
authors: Y
authors: Xie
authors: Bo
authors: B
authors: Yuan
authors: Wei
authors: W
authors: Zhang
authors: Xingyu
authors: X
authors: Jiang
mesh_terms: D000818:Animals; D002452:Cell Count; D002465:Cell Movement; D016000:Cluster Analysis; D009415:Nerve Net / Q000502:physiology*; D016501:Neurites / Q000378:metabolism; D009474:Neurons / Q000166:cytology*; D009928:Organ Specificity; D051381:Rats; D017207:Rats, Sprague-Dawley; D013499:Surface Properties; D013997:Time Factors