title: Divergent Hox Coding and Evasion of Retinoid Signaling Specifies Motor Neurons Innervating Digit Muscles.
abstract: The establishment of spinal motor neuron subclass diversity is achieved through developmental programs that are aligned with the organization of muscle targets in the limb. The evolutionary emergence of digits represents a specialized adaptation of limb morphology, yet it remains unclear how the specification of digit-innervating motor neuron subtypes parallels the elaboration of digits. We show that digit-innervating motor neurons can be defined by selective gene markers and distinguished from other LMC neurons by the expression of a variant Hox gene repertoire and by the failure to express a key enzyme involved in retinoic acid synthesis. This divergent developmental program is sufficient to induce the specification of digit-innervating motor neurons, emphasizing the specialized status of digit control in the evolution of skilled motor behaviors. Our findings suggest that the emergence of digits in the limb is matched by distinct mechanisms for specifying motor neurons that innervate digit muscles.
authors.affiliation: Howard Hughes Medical Institute, Kavli Institute for Brain Science, Zuckerman Mind Brain Behavior Institute, Departments of Neuroscience and Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA.
authors.forename: Alana I
authors.initials: AI
authors.lastname: Mendelsohn
authors.affiliation: NYU Neuroscience Institute, Department of Neuroscience and Physiology, New York University School of Medicine, New York, NY 10016, USA.
authors.forename: Jeremy S
authors.initials: JS
authors.lastname: Dasen
authors.affiliation: Howard Hughes Medical Institute, Kavli Institute for Brain Science, Zuckerman Mind Brain Behavior Institute, Departments of Neuroscience and Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA. Electronic address: tmj1@columbia.edu.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Jessell
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology; D005121:Extremities / Q000294:innervation*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D018398:Homeodomain Proteins / Q000378:metabolism; D051379:Mice; D009046:Motor Neurons / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D012176:Retinoids / Q000378:metabolism*; D015398:Signal Transduction; D013116:Spinal Cord / Q000378:metabolism
chemical_list: D018398:Homeodomain Proteins; D012176:Retinoids
keywords: Hox proteins; cell identity; development; digits; motor control; motor neuron; retinoid signaling; spinal cord