Establishing Neuronal Polarity with Environmental and Intrinsic Mechanisms

Abstract

Neurons are among the most morphologically complex cells. A distinction between two compartments, axon and dendrite, generates cellular domains that differ in membrane composition and cytoskeletal structure, and sets the platform on which morphogens, transcription programs, and synaptic activity sculpt neuronal form. The establishment of this distinction, called Neuronal Polarity, entails interpreting spatial and intrinsic cues and converting them to cytoskeletal rearrangements that give rise to axons and dendrites. Hence, this early developmental event underpins the future functional properties of the neuron to receive and transmit information. Here we review the current understanding of developmental cues and cell biological mechanisms that establish polarity in newborn neurons, synthesizing information from vertebrate and invertebrate model systems.

Regulation of neuronal development and function by ROS

“…Characteristically, axons contain microtubules whose plus ends face away from the cell body, while dendrites have microtubules of mixed (mammals) or opposite polarity (e.g. Drosophila and Caenorhabditis elegans ; for reviews see ). Perhaps inspired by work from other systems that have associated NADPH oxidase‐generated ROS with the regulation of cell polarisation and growth, for example, Arabidopsis hair cell outgrowth and the enforcement of apical dominance in Aspergillus hyphae , ROS have been investigated as signals regulating the polarisation of neurons.…”

“…The activity of protein kinases is critical during cellular polarisation, meditating positive feedback loops and signal amplification. Multiple pathways converge onto PI3 kinase, which is enriched at the tip of the future axon as neurons adopt a polarised morphology (reviewed in ). Interestingly, PI3 kinase signalling can be regulated by ROS, by redox‐mediated inhibition of the phosphatase and tensin homolog (PTEN), which antagonises the PI3 kinase product phosphoinositide‐3‐phosphate .…”

“…It also suggests that ROS might have a modulatory role rather than being critically required for the establishment of neuronal polarity. This would not be entirely surprising, as during nervous system development neural progenitor cells and their progeny are invariably located within asymmetric environments where local enrichment of numerous cues, including cell adhesion and extracellular matrix proteins, can contribute to cellular polarisation (for review see ).…”

Tuba activates Cdc42 during neuronal polarization downstream of the small GTPase Rab8a

“…Neurons en route toward the apical surface of the cortex displayed a distinctive migration morphology characterized as bipolar, with a leading process that later developed into apical dendrites and a trailing process that is initially specified as the axon (Yogev and Shen, 2017). Therefore, we analyzed the presence and prevalence of multipolar and bipolar GFP-positive neurons in the SVZ-IZ area in control and Rab8a T22N or Rab8a Q67L mutants ( Figure 7A-B, D).…”

Role of mechanical cues in shaping neuronal morphology and connectivity

“…The process by which one of these neurites starts acquiring the identity and characteristics of an axon is referred to as axon specification, a key symmetry‐breaking event which initiates neuronal polarisation. Depending on the experimental context, this process has been shown to result from the interpretation of cell‐intrinsic and/or extrinsic signals [reviewed in Yogev and Chen, ]. Lamoureux et al.…”