Regulation of dendrite morphogenesis by extrinsic cues

doi:10.1016/j.tins.2015.05.003

Trends in Neurosciences

Volume 38, Issue 7, July 2015, Pages 439-447

https://doi.org/10.1016/j.tins.2015.05.003 Get rights and content

Highlights

•
Extrinsic cues regulate distinct phases of dendrite morphogenesis.
•
Dendrite development requires secreted proteins, contact-mediated regulators, and neuronal activity.
•
Extrinsic cues influence local and global mechanisms of dendrite development.

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.

Section snippets

Extrinsic cues regulate distinct steps in dendrite morphogenesis

To establish proper connectivity, dendrites transition through fundamental developmental stages from growth and guidance, to branching and pruning, to self-avoidance and tiling. The regulation of dendrite patterning can be broadly divided into cell-extrinsic and cell-intrinsic mechanisms. In the nervous system, cell-extrinsic cues consist of secreted or transmembrane signals as well as neuronal activity in response to trans-synaptic transmission. By contrast, cell-intrinsic pathways represent

Neurotrophins

Neurotrophins represent a family of secreted proteins, consisting of nerve growth factor (NGF), brain-derived growth factor (BDNF), neurotrophin 3 (NT-3), and neurotrophin 4 (NT-4), that act on neurons through members of the tyrosine receptor kinase (Trk) family [4]. In the rodent cerebral cortex, neurotrophins promote dendrite growth and arborization, but this effect varies depending on the specific neurotrophin, cortical layer, and location of the dendrites [5].

Specific deletion of the BDNF

Cadherins and protocadherins

Cell adhesion molecules such as the cadherin Flamingo (Fmi) as well as the protocadherins and atypical cadherins are crucial for dendrite tiling, self-avoidance, and arbor homeostasis 46, 47. In Drosophila, Fmi forms a complex with the LIM domain protein Espinas (Esn) in class IV dendritic arborization (da) neurons [48]. Genetic evidence suggests that Fmi–Esn signal downstream to molecules regulating cell polarity such as Van Gogh (Vang) and Rho, two proteins essential for self-avoidance.

Neuronal activity and calcium signaling

In addition to secreted and contact-mediated regulators, neuronal activity represents a key cue in the regulation of dendrite development. The effects of neuronal activity on dendrite development are mediated by calcium signals 76, 77. Recent studies have revealed that calcium transients promote dendrite pruning in Drosophila sensory neurons. Voltage-gated calcium channels (VGCCs) are responsible for generating compartmentalized calcium transients, and the calcium-activated protease calpain

Concluding remarks and future perspectives

During the past two decades, investigations of dendrite development have uncovered an enormously complex set of extrinsic cues and associated signaling mechanisms that regulate dendrite morphogenesis. We have discussed the major categories of regulators including secreted factors, contact-mediated cues, and neuronal activity as major extrinsic drivers of dendrite morphogenesis. A key observation emerging from these studies is that extrinsic cues regulate far more than dendrite morphogenesis,

Acknowledgments

This work was supported by the National Institutes of Health grant NS084393 (to A.B.) and by the European Molecular Biology Organization (ALTF 889-2011 to P.V.). We thank members of the laboratory of A.B. for helpful discussions and critical reading of the manuscript.

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^*: These authors contributed equally to the manuscript.

^‡: Current address: Department of Otolaryngology, Massachusetts Eye and Ear Infirmary and Harvard Medical School, Boston, MA 02114, USA.

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Trends in Neurosciences

ReviewRegulation of dendrite morphogenesis by extrinsic cues

Highlights

Section snippets

Extrinsic cues regulate distinct steps in dendrite morphogenesis

Neurotrophins

Cadherins and protocadherins

Neuronal activity and calcium signaling

Concluding remarks and future perspectives

Acknowledgments

Curr. Opin. Neurobiol.

Neuron

Neuron

Cell Rep.

Neuron

Neuron

Cell

Neuron

Neuron

Neuron

Neuron

Neuron

Cell

Mol. Cell. Neurosci.

Neuron

Cell

Dev. Cell

Neuron

Neuron

Schizophr. Res.

Neuron

Curr. Biol.

Cell

Neuron

Cell

Cell

Neuron

Neuron

Cell

Cell

Neuron

Neuron

Neuron

Brain Res. Brain Res. Protoc.

Neuron

Neuron

Semin. Cell Dev. Biol.

Cell Rep.

Neuron

Neuron

Cell-intrinsic drivers of dendrite morphogenesis

Development

Neurotrophins: roles in neuronal development and function

Annu. Rev. Neurosci.

Trk receptors: roles in neuronal signal transduction

Annu. Rev. Biochem.

Truncated and full-length TrkB receptors regulate distinct modes of dendritic growth

Nat. Neurosci.

Dendrite morphogenesis depends on relative levels of NT-3/TrkC signaling

Science

Activity-dependent regulation of dendritic growth and maintenance by glycogen synthase kinase 3beta

Nat. Commun.

Semaphorin 3A is a chemoattractant for cortical apical dendrites

Nature

Increased proximal bifurcation of CA1 pyramidal apical dendrites in sema3A mutant mice

J. Comp. Neurol.

Autism spectrum disorder susceptibility gene TAOK2 affects basal dendrite formation in the neocortex

Nat. Neurosci.

Review
Regulation of dendrite morphogenesis by extrinsic cues