Abstract
Neuronal dendrites dynamically protrude many fine filopodia in the early stages of neuronal development and gradually establish complex structures. The importance of the dendritic filopodia in the formation of axo-dendritic connections is established, but their role in dendrite morphogenesis remains unknown. Using time-lapse imaging of cultured rat hippocampal neurons, we revealed here that many filopodia dynamically protruded from dendrites and transiently interacted with each other to form dendritic filopodia-filopodia contacts in the early stages of neuronal development. The MAGUK family member, Zonula Occludens-1 (ZO-1), which is known to be associated with the nectin and cadherin cell adhesion systems, was concentrated at these dendritic filopodia-filopodia contact sites and also at the tips of free dendritic filopodia. Overexpression of ZO-1 increased the formation of dendritic filopodia and their interactions, and induced abnormal dendrite morphology. Conversely, knockdown of ZO-1 decreased the formation of dendritic filopodia and their interactions, and induced abnormal dendrite morphology which was different from that induced by the overexpression of ZO-1. The components of the nectin and cadherin systems were co-localized with ZO-1 at the dendritic filopodia-filopodia contact sites, but not at the tips of free dendritic filopodia. Overexpression of ZO-1 increased the accumulation of these cell adhesive components at the dendritic filopodia-filopodia contact sites and stabilized their interactions, whereas knockdown of ZO-1 reduced their accumulation at the dendritic filopodia-filopodia contact sites. These results indicate that ZO-1 regulates dendritic filopodial dynamics, which is implicated in dendrite morphogenesis cooperatively with the nectin and cadherin systems in cultured neurons.
Highlights
Developing neurons elongate an axon that attaches to the dendrites of other neurons to form synapses and establish neuronal networks
We found that most dendritic filopodia that did not interact with axons dynamically protruded and transiently interacted with each other to form dendritic filopodia-filopodia contacts, and that Zonula Occludens-1 (ZO-1) plays a role in dendrite morphogenesis cooperatively with the nectin and cadherin systems by regulating these dynamic behaviors of dendritic filopodia in cultured neurons
It was previously shown by time-lapse fluorescence microscopy of developing hippocampal tissue slices that many fine filopodia dynamically protruded from the dendrites of pyramidal neurons, and that some of them interacted with axons to form synapses [12,13]
Summary
Developing neurons elongate an axon that attaches to the dendrites of other neurons to form synapses and establish neuronal networks. Dendrites are branched and show complex structures with arbors of different sizes and shapes depending on the type of neurons [1,2]. Transcriptional regulators, cytoskeletal regulators, motors, cell surface receptors, cell adhesion molecules (CAMs), and extracellular signaling molecules secreted from cells have been shown to regulate dendrite growth and morphology. Of these mechanisms, cytoskeletal regulators such as the Cdc, Rac and Rho small G proteins regulate dendrite growth and morphology through the reorganization of the actin cytoskeleton [7]. How dendritic arbors take shape is still largely unknown
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