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The Paired Homeodomain Protein DRG11 Is Required for the Projection of Cutaneous Sensory Afferent Fibers to the Dorsal Spinal Cord

Chen, Zhou-Feng and Rebelo, Sandra and White, Fletcher and Malmberg, Annika B. and Baba, Hiroshi and Lima, Deolinda and Woolf, Clifford J. and Basbaum, Allan I. and Anderson, David J. (2001) The Paired Homeodomain Protein DRG11 Is Required for the Projection of Cutaneous Sensory Afferent Fibers to the Dorsal Spinal Cord. Neuron, 31 (1). pp. 59-73. ISSN 0896-6273. https://resolver.caltech.edu/CaltechAUTHORS:20150302-160441606

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Abstract

Cutaneous sensory neurons that detect noxious stimuli project to the dorsal horn of the spinal cord, while those innervating muscle stretch receptors project to the ventral horn. DRG11, a paired homeodomain transcription factor, is expressed in both the developing dorsal horn and in sensory neurons, but not in the ventral spinal cord. Mouse embryos deficient in DRG11 display abnormalities in the spatio-temporal patterning of cutaneous sensory afferent fiber projections to the dorsal, but not the ventral spinal cord, as well as defects in dorsal horn morphogenesis. These early developmental abnormalities lead, in adults, to significantly attenuated sensitivity to noxious stimuli. In contrast, locomotion and sensori-motor functions appear normal. Drg11 is thus required for the formation of spatio-temporally appropriate projections from nociceptive sensory neurons to their central targets in the dorsal horn of the spinal cord.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1016/S0896-6273(01)00341-5DOIArticle
http://www.sciencedirect.com/science/article/pii/S0896627301003415PublisherArticle
http://www.sciencedirect.com/science/article/pii/S0896627301003415#section_lbl5PublisherSupporting Information
Additional Information:© 2001 Cell Press. Received October 24, 2000; Revised April 18, 2001. We thank Shirley Pease and the staff of TAFCIT for production and maintenance of mutant mice, Gaby Mosconi for laboratory management, Heather Gilbert for technical help, Richard Behringer for AB-1 ES cells and STO cells, P. Mombaerts for the IRES-Tau-lacZ plasmid, Louis F. Reichardt and David Julius for antibodies, Marc Tessier-Lavigne for Slit and netrin probes, Haiming Xu for assistance with RT-PCR experiments, T. Saito for Figure 2, and Artur Kania, Tom Jessell, and Randy Johnson for sharing unpublished data on the Lmx1b knockout and for providing various probes and reagents. We are grateful to Tom Jessell for helpful comments on the manuscript. Animal experiments were reviewed and approved by the Animal Use and Care Committees (IACUCs) at Caltech and at UCSF. S.R. was supported in the laboratory of D.J.A. by a Gulbenkian Foundation Fellowship. Supported by NIH grant NS38253-01 to C.J.W. and NS 14627 to A.I.B. D.J.A. is an Investigator of the Howard Hughes Medical Institute.
Funders:
Funding AgencyGrant Number
Gulbenkian Foundation FellowshipUNSPECIFIED
NIHNS38253-01
NIHNS14627
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
Issue or Number:1
Record Number:CaltechAUTHORS:20150302-160441606
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20150302-160441606
Official Citation:Chen, Z.-F., Rebelo, S., White, F., Malmberg, A. B., Baba, H., Lima, D., . . . Anderson, D. J. (2001). The Paired Homeodomain Protein DRG11 Is Required for the Projection of Cutaneous Sensory Afferent Fibers to the Dorsal Spinal Cord. Neuron, 31(1), 59-73. doi: http://dx.doi.org/10.1016/S0896-6273(01)00341-5
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:55435
Collection:CaltechAUTHORS
Deposited By: Joanne McCole
Deposited On:03 Mar 2015 16:02
Last Modified:03 Oct 2019 08:05

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