Molecular mechanisms of dendrite morphogenesis

Abstract

Dendrites are key integrators of synaptic information in neurons and play vital roles in neuronal plasticity. Hence, it is necessary that dendrite arborization is precisely controlled and coordinated with synaptic activity to ensure appropriate functional neural network integrity. In the past several years, it has become increasingly clear that several cell intrinsic and extrinsic mechanisms contribute to dendritic arborization. In this review, we will discuss some of the molecular mechanisms that regulate dendrite morphogenesis, particularly in cortical and hippocampal pyramidal neurons and some of the implications of aberrant dendritic morphology for human disease. Finally, we will discuss the current challenges and future directions in the field.

Keywords: aberrant dendritic morphology; arborization; dendrite; molecular mechanims; plasticity and learning.

Figure 1

Synaptic terminals on dendrites and schematic of excitatory and inhibitory synapses: rat hippocampal neurons in culture (DIV 17) transfected with GFP (green) and immunostained with markers that label presynaptic terminals of either excitatory (top, red—vGlut1) or inhibitory (bottom, red—GAD65) synapses. Note that the excitatory synapses predominantly form on spine heads, while the inhibitory synapses are predominantly localized in the dendritic shaft. The presynaptic terminals contain neurotransmitter loaded vesicles, while the postsynaptic region harbors neurotransmitter receptors.

Figure 2

Schematic of neuron showing various classes of molecules with some of the more recent examples that have been implicated in dendrite arborization.

Figure 3

Four examples of molecules from different classes that regulate dendritic branching. Knockdown of the postsynaptic density proteins, Erbin (DIV 11–17) or regulator of postsynaptic proteins, Cypin (DIV 5–10), or a component of the Cadherin-Catenin cell adhesion complex, δ-catenin (DIV 11–17) result in a compromise in dendritic branching. However, the addition of BDNF (25 ng/ml at DIV 7–10) to hippocampal neurons increases neurite outgrowth and branching.