Motor neuron columnar fate imposed by sequential phases of Hox-c activity.
The organization of neurons into columns is a prominent feature of central nervous system structure and function. In many regions of the central nervous system the grouping of neurons into columns links cell-body position to axonal trajectory, thus contributing to the establishment of topographic neural maps. This link is prominent in the developing spinal cord, where columnar sets of motor neurons innervate distinct targets in the periphery. We show here that sequential phases of Hox-c protein expression and activity control the columnar differentiation of spinal motor neurons. Hox expression in neural progenitors is established by graded fibroblast growth factor signalling and translated into a distinct motor neuron Hox pattern. Motor neuron columnar fate then emerges through cell autonomous repressor and activator functions of Hox proteins. Hox proteins also direct the expression of genes that establish motor topographic projections, thus implicating Hox proteins as critical determinants of spinal motor neuron identity and organization.
Howard Hughes Medical Institute, Department of Biochemistry and Molecular Biophysics, Center for Neurobiology and Behavior, Columbia University, 701 West 168th Street, New York, New York 10032, USA. jd2009@columbia.edu
Jeremy S
JS
Dasen
Jeh-Ping
JP
Liu
Thomas M
TM
Jessell
D000818:Animals; D019521:Body Patterning / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002642:Chick Embryo; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D051524:Fibroblast Growth Factor 8; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008938:Mitosis; D009046:Motor Neurons / Q000166:cytology* / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013116:Spinal Cord / Q000166:cytology* / Q000187:drug effects / Q000196:embryology / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
D004268:DNA-Binding Proteins; C496457:Fgf8 protein, mouse; C491257:HOXB9 protein, human; D018398:Homeodomain Proteins; C104161:Hoxb9 protein, mouse; C080041:Hoxc6 protein, mouse; C065404:Hoxc9 protein, mouse; C490282:Hoxd9 protein, mouse; D009363:Neoplasm Proteins; D012333:RNA, Messenger; C097899:homeobox protein HOXA9; D051524:Fibroblast Growth Factor 8; D005346:Fibroblast Growth Factors