Hox repertoires for motor neuron diversity and connectivity gated by a single accessory factor, FoxP1.
The precision with which motor neurons innervate target muscles depends on a regulatory network of Hox transcription factors that translates neuronal identity into patterns of connectivity. We show that a single transcription factor, FoxP1, coordinates motor neuron subtype identity and connectivity through its activity as a Hox accessory factor. FoxP1 is expressed in Hox-sensitive motor columns and acts as a dose-dependent determinant of columnar fate. Inactivation of Foxp1 abolishes the output of the motor neuron Hox network, reverting the spinal motor system to an ancestral state. The loss of FoxP1 also changes the pattern of motor neuron connectivity, and in the limb motor axons appear to select their trajectories and muscle targets at random. Our findings show that FoxP1 is a crucial determinant of motor neuron diversification and connectivity, and clarify how this Hox regulatory network controls the formation of a topographic neural map.
Dasen
Jeremy S
JS
Smilow Neuroscience Program, Department of Physiology and Neuroscience, New York University School of Medicine, New York, NY 10016, USA. jeremy.dasen@nyumc.org
De Camilli
Alessandro
A
Wang
Bin
B
Tucker
Philip W
PW
Jessell
Thomas M
TM
D000818:Animals; D002454:Cell Differentiation; D002642:Chick Embryo; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D018398:Homeodomain Proteins / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000166:cytology / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D013116:Spinal Cord / Q000166:cytology / Q000378:metabolism*
D051858:Forkhead Transcription Factors; C432917:Foxp1 protein, mouse; D018398:Homeodomain Proteins; D012097:Repressor Proteins; D049452:Green Fluorescent Proteins