Regulation of dendrite morphogenesis by extrinsic cues

Abstract

Dendrites play a central role in the integration and flow of information in the nervous system. The morphogenesis and maturation of dendrites is hence an essential step in the establishment of neuronal connectivity. Recent studies have uncovered crucial functions for extrinsic cues in the development of dendrites. We review the contribution of secreted polypeptide growth factors, contact-mediated proteins, and neuronal activity in distinct phases of dendrite development. We also highlight how extrinsic cues influence local and global intracellular mechanisms of dendrite morphogenesis. Finally, we discuss how these studies have advanced our understanding of neuronal connectivity and have shed light on the pathogenesis of neurodevelopmental disorders.

Keywords: calcium signaling; contact-mediated regulators; dendrite morphogenesis; neuronal activity; secreted polypeptide growth factors.

Figure 1. Diverse patterns of dendrite branching in different type of neurons

(A) Mouse cerebellar granule neuron have only four to five dendrites, each of which ends with a dendritic claw that harbors postsynaptic dendritic specializations. (B) Elaborate dendritic tree in a mouse Purkinje cell. (C) Mouse hippocampal pyramidal neuron characterized by two distinct dendritic trees, the basal and apical dendrites. (D) Dendritic tree in Caenorhabditis elegans PVD neuron. (E) Multidendritic class IV da neuron in Drosophila melanogaster.

Figure 2. Cell-extrinsic regulators of dendrite morphogenesis

Summary of molecules regulating different stages of dendrite development, as described in the text. *Molecules that mediate repulsion between sister dendrites.

Figure 3. Effects of calcium signaling on dendrite morphogenesis

Calcium influx from voltage-gated calcium channels VGCCs or NMDA receptors (NMDAR) activates several CaMK family members and MAPKs which in turn regulate dendrite growth and elaboration. VGCC are also responsible to generate compartmentalized calcium transients to trigger dendrite pruning. In later stage of dendrite development, CaMKIIβ activated by calcium influx from TRPC5 channel drives dendrite pruning.