From Motor Neuron Specification to Function: Filling in the Gaps

Abstract

Motor neurons operate at the interface between nervous system and movement apparatus and play several roles in movement generation. During development, motor neurons emerge from progenitor cells in the ventral neural tube and eventually settle into stereotypic position that predict the identity of their target muscles. The specification of these ‘positional’ identities has been studied in detail and involves a coordinate grid of intersecting extrinsic signals that result in the activation of unique combinations of transcription factors acting as cell-autonomous determinants. Eventually, motor neurons diversify into ‘functional’ (e.g., fast/intermediate/slow alpha, beta, and gamma) subtypes essential for proper movement execution, a process linked to the acquisition of unique sets of functional properties. Recent progress has provided insights into the molecular composition and specification of motor neuron functional identities, but little is known about their relationship to the mechanisms underlying the specification of positional identities. In this chapter, we attempt to provide a framework for consolidating both aspects of motor neuron diversification, in addition to outlining the gaps in our knowledge to guide future research directions aiming at understanding the events on a motor neuron’s journey from specification to function.