Proper development of relay somatic sensory neurons and D2/D4 interneurons requires homeobox genes Rnx/Tlx-3 and Tlx-1.
Trigeminal nuclei and the dorsal spinal cord are first-order relay stations for processing somatic sensory information such as touch, pain, and temperature. The origins and development of these neurons are poorly understood. Here we show that relay somatic sensory neurons and D2/D4 dorsal interneurons likely derive from Mash1-positive neural precursors, and depend on two related homeobox genes, Rnx and Tlx-1, for proper formation. Rnx and Tlx-1 maintain expression of Drg11, a homeobox gene critical for the development of pain circuitry, and are essential for the ingrowth of trkA+ nociceptive/thermoceptive sensory afferents to their central targets. We showed previously that Rnx is necessary for proper formation of the nucleus of solitary tract, the target for visceral sensory afferents. Together, our studies demonstrate a central role for Rnx and Tlx-1 in the development of two major classes of relay sensory neurons, somatic and visceral.
Qian
Ying
Y
The Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
Shirasawa
Senji
S
Chen
Chih-Li
CL
Cheng
Leping
L
Ma
Qiufu
Q
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D001921:Brain / Q000196:embryology / Q000378:metabolism*; D001973:Bromodeoxyuridine; D002454:Cell Differentiation; D002470:Cell Survival; D017931:DNA Primers / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D017403:In Situ Hybridization; D020287:In Situ Nick-End Labeling; D007395:Interneurons / Q000502:physiology*; D051379:Mice; D008817:Mice, Mutant Strains; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D009475:Neurons, Afferent / Q000502:physiology*; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D010146:Pain / Q000378:metabolism / Q000503:physiopathology; D016133:Polymerase Chain Reaction; D013116:Spinal Cord / Q000166:cytology / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
D051792:Basic Helix-Loop-Helix Proteins; D001973:Bromodeoxyuridine; D017931:DNA Primers; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D015513:Oncogene Proteins; D014157:Transcription Factors; C499317:Ascl1 protein, mouse; C487378:Tlx1 protein, mouse