Neuritogenesis

Neuritogenesis is the process by which developing neurons form neurites, which are the initial protrusions that will become axons and dendrites. This stage establishes neuronal polarity and the basic architecture for synaptic connections. Neuritogenesis occurs during early neural development and can also be involved in regenerative processes after injury or in culture systems.

The process unfolds in several stages. First, neurite initiation involves local remodeling of the actin cytoskeleton at specific sites on the neuronal soma, followed by membrane addition and stabilization of short protrusions. Next, neurites elongate as microtubules extend into the growing processes, with growth cones at their tips navigating the extracellular environment. Growth cones explore guidance cues and substrates, determining directionality and branching. As cells mature, one process typically becomes the axon while others become dendrites, establishing neuronal polarity.

Key molecular mechanisms coordinate cytoskeletal dynamics and signaling. Rho family GTPases—Rac1 and Cdc42 promote actin remodeling and extension, whereas RhoA can restrict growth. Intracellular polarity cues involve the Par3/Par6/aPKC complex and related kinases (such as SAD kinases) that help stabilize axonal identity. Signaling pathways including PI3K-Akt and mTOR influence growth and differentiation. Extracellular cues from guidance molecules—netrins, semaphorins, ephrins, and slits—along with adhesion molecules like integrins, shape growth cone navigation and neurite pathfinding.

Neuritogenesis underpins proper brain development and the establishment of functional circuits. Disruptions are associated with neurodevelopmental disorders, while understanding neuritogenesis informs regenerative strategies and neuronal tissue engineering. Experimental studies rely on cultured neurons and in vivo models to dissect the interplay of intrinsic programs and extrinsic signals guiding neurite formation.