The Paired Homeodomain Protein DRG11 Is Required for the Projection of Cutaneous Sensory Afferent Fibers to the Dorsal Spinal Cord
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.
Additional Information
© 2001 Cell Press. Under an Elsevier user license. 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assistance with RT-PCR experiments, T. Saito for Figure 2, and Artur Kania, Tom Jessell, and Randy Johnson for sharing unpublished data on the Lmx1b knockout and for providing various probes and reagents.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.Files
Additional details
- Eprint ID
- 55435
- Resolver ID
- CaltechAUTHORS:20150302-160441606
- Gulbenkian Foundation Fellowship
- NS38253-01
- NIH
- NS14627
- NIH
- Howard Hughes Medical Institute (HHMI)
- Created
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2015-03-03Created from EPrint's datestamp field
- Updated
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2021-11-10Created from EPrint's last_modified field