Neural Orchestration of Mandibular Development.

The mandible, exclusively innervated by the trigeminal nerve and influenced by intricate biomechanical factors, serves as a vital model for studying neuro-osseous interactions in craniofacial development. However, research on its neural regulation is comparatively weak relative to the appendicular skeleton. This review aims to consolidate emerging evidence regarding the neural regulation of mandibular morphogenesis, emphasizing mechanisms that differ from those of long bones, and to highlight its clinical significance. A comprehensive review was conducted across a broad array of databases, including PubMed, Scopus, Google Scholar, Web of Science, Embase, IEEE Xplore, and the Cochrane Library, without time restriction. The goal was to synthesize current findings on the neuro-bone interplay specific to the mandible. The review identifies that peripheral innervation, involving autonomous and sensory nerves, regulates mandibular osteogenesis via spatially distinct neurotransmitter signalling. Furthermore, axon guidance molecules and neurotrophic factors establish precise neurovascular patterning during development and facilitate reparative processes. The key role of nerve-bone communication in mandible is highlighted. We encourage deeper research into its unique biology to support the development of precise treatments for neurodevelopmental disorders and maxillofacial malformations.