Molecular mechanisms regulating motor neuron development and degeneration

Motor neurons are a well-defined, although heterogeneous group of cells res ponsible for transmitting information from the central nervous system to th e locomotor system. Spinal motor neurons are specified by soluble factors p roduced by structures adjacent to the primordial spinal cord, signaling thr ough homeodomain proteins. Axonal pathfinding is regulated by cell-surface receptors that interact with extracellular ligands and once synaptic connec tions have formed, the survival of the somatic motor neuron is dependent on the provision of target-derived growth factors, although nontarget-derived factors, produced by either astrocytes or Schwann cells, are also potentia lly implicated. Somatic motor neuron degeneration leads to profound disabil ity, and multiple pathogenetic mechanisms including aberrant growth factor signaling, abnormal neurofilament accumulation, excitotoxicity, and autoimm unity have been postulated to be responsible. Even when specific deficits h ave been identified, for example, mutations of the superoxide dismutase-l g ene in familial amyotrophic sclerosis and polyglutamine expansion of the an drogen receptor in spinal and bulbar muscular atrophy, the mechanisms by wh ich somatic motor neuronal degeneration occurs remain unclear. In order to treat motor system degeneration effectively, we will need to understand the se mechanisms more thoroughly.