Regulation of motor neuron subtype identity by repressor activity of Mnx class homeodomain proteins.
In the developing spinal cord, motor neurons acquire columnar subtype identities that can be recognized by distinct profiles of homeodomain transcription factor expression. The mechanisms that direct the differentiation of motor neuron columnar subtype from an apparently uniform group of motor neuron progenitors remain poorly defined. In the chick embryo, the Mnx class homeodomain protein MNR2 is expressed selectively by motor neuron progenitors, and has been implicated in the specification of motor neuron fate. We show here that MNR2 expression persists in postmitotic motor neurons that populate the median motor column (MMC), whereas its expression is rapidly extinguished from lateral motor column (LMC) neurons and from preganglionic autonomic neurons of the Column of Terni (CT). The extinction of expression of MNR2, and the related Mnx protein HB9, from postmitotic motor neurons appears to be required for the generation of CT neurons but not for LMC generation. In addition, MNR2 and HB9 are likely to mediate the suppression of CT neuron generation that is induced by the LIM HD protein Lim3. Finally, MNR2 appears to regulate motor neuron identity by acting as a transcriptional repressor, providing further evidence for the key role of transcriptional repression in motor neuron specification.
William
Christopher M
CM
Howard Hughes Medical Institute, Department of Biochemistry and Molecular Biophysics, Center for Neurobiology and Behavior, Columbia University, 701 West 168 Street, New York, NY 10032, USA.
Tanabe
Yasuto
Y
Jessell
Thomas M
TM
D000595:Amino Acid Sequence; D000818:Animals; D015415:Biomarkers; D055417:Bone Morphogenetic Protein 5; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D002642:Chick Embryo; D005786:Gene Expression Regulation; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D008938:Mitosis; D008953:Models, Anatomic; D008969:Molecular Sequence Data; D009046:Motor Neurons / Q000145:classification / Q000166:cytology / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D013116:Spinal Cord / Q000166:cytology* / Q000254:growth & development / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
D015415:Biomarkers; D055417:Bone Morphogenetic Protein 5; D019485:Bone Morphogenetic Proteins; D018398:Homeodomain Proteins; C115037:MNR2 protein, vertebrate; D009419:Nerve Tissue Proteins; D012097:Repressor Proteins; D014157:Transcription Factors