Abstract
The development of the dendritic arbor in pyramidal neurons is critical for neural circuit function. Here, we uncovered a pathway in which δ-catenin, a component of the cadherin-catenin cell adhesion complex, promotes coordination of growth among individual dendrites and engages the autophagy mechanism to sculpt the developing dendritic arbor. Using a rat primary neuron model, time-lapse imaging, immunohistochemistry, and confocal microscopy, we found that apical and basolateral dendrites are coordinately sculpted during development. Loss or knockdown of δ-catenin uncoupled this coordination, leading to retraction of the apical dendrite without altering basolateral dendrite dynamics. Autophagy is a key cellular pathway that allows degradation of cellular components. We observed that the impairment of the dendritic arbor resulting from δ-catenin knockdown could be reversed by knockdown of autophagy-related 7 (ATG7), a component of the autophagy machinery. We propose that δ-catenin regulates the dendritic arbor by coordinating the dynamics of individual dendrites and that the autophagy mechanism may be leveraged by δ-catenin and other effectors to sculpt the developing dendritic arbor. Our findings have implications for the management of neurological disorders, such as autism and intellectual disability, that are characterized by dendritic aberrations.
Highlights
In pyramidal neurons of the hippocampus and cortex, dendrites are the major sites of information input [1, 2]
Overall, during the time period between DIV 11 and 19, both primary and secondary dendrites had net extension (Fig. 1D) and similar levels of average extension (Fig. 1E). These data suggest that in this model system, DIV 11–14 represents a period of dynamic dendrite extension, whereas both extension and retraction are balanced at DIV 14–19, leading to overall dendrite extension
To begin to evaluate whether the autophagy pathway might be involved in dendritic arborization during development, we examined whether major mediators of the autophagy pathway were expressed in the hippocampus and cortex during development
Summary
In pyramidal neurons of the hippocampus and cortex, dendrites are the major sites of information input [1, 2]. We provide evidence to demonstrate that d-catenin promotes coordinated development of the apical and basolateral dendrites in primary neurons and engages the autophagy mechanism to sculpt the developing dendritic arbor. To examine which of these mechanisms is responsible, we examined the development of the dendritic arbor in primary neurons expressing vector or a previously validated [32, 59] shRNA to d-catenin by time-lapse analysis (Fig. 3A).
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