Recent advances in branching mechanisms underlying neuronal morphogenesis

Abstract

Proper neuronal wiring is central to all bodily functions, sensory perception, cognition, memory, and learning. Establishment of a functional neuronal circuit is a highly regulated and dynamic process involving axonal and dendritic branching and navigation toward appropriate targets and connection partners. This intricate circuitry includes axo-dendritic synapse formation, synaptic connections formed with effector cells, and extensive dendritic arborization that function to receive and transmit mechanical and chemical sensory inputs. Such complexity is primarily achieved by extensive axonal and dendritic branch formation and pruning. Fundamental to neuronal branching are cytoskeletal dynamics and plasma membrane expansion, both of which are regulated via numerous extracellular and intracellular signaling mechanisms and molecules. This review focuses on recent advances in understanding the biology of neuronal branching.

Keywords: actin; activity; arborization; branching; exocytosis; gene expression; microtubules.

Figure 1.. Hierarchical events of neuronal branching.

Neuronal branching is a coordinated process that requires extensive filamentous actin and microtubule (MT) reorganization and plasma membrane expansion, depicted in the center of the branching hierarchy. These foundational events are spatially and temporally regulated by numerous signaling and mechanical pathways in a coordinated fashion. These pathways are initiated in response to synaptic activity, extracellular guidance molecules, neurotrophic factors, or adhesive ligands. This outside-in signaling results in extensive cytoskeletal and membrane changes regulated directly through signal transduction, transport and sorting of organelles and cargo-carrying vesicles, and energy production or indirectly through gene expression changes via transcriptional regulation, epigenetic modifications, post-transcriptional and post-translational modifications (PTMs), and local protein synthesis.