title: Ontogeny of excitatory spinal neurons processing distinct somatic sensory modalities.
abstract: Spatial and temporal cues govern the genesis of a diverse array of neurons located in the dorsal spinal cord, including dI1-dI6, dIL(A), and dIL(B) subtypes, but their physiological functions are poorly understood. Here we generated a new line of conditional knock-out (CKO) mice, in which the homeobox gene Tlx3 was removed in dI5 and dIL(B) cells. In these CKO mice, development of a subset of excitatory neurons located in laminae I and II was impaired, including itch-related GRPR-expressing neurons, PKCγ-expressing neurons, and neurons expressing three neuropeptide genes: somatostatin, preprotachykinin 1, and the gastrin-releasing peptide. These CKO mice displayed marked deficits in generating nocifensive motor behaviors evoked by a range of pain-related or itch-related stimuli. The mutants also failed to exhibit escape response evoked by dynamic mechanical stimuli but retained the ability to sense innocuous cooling and/or warm. Thus, our studies provide new insight into the ontogeny of spinal neurons processing distinct sensory modalities.
authors.affiliation: Dana-Farber Cancer Institute and Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, Department of Neuroscience, Max Delbrück Center, 13125 Berlin, Germany, and Institute of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Xu
authors.forename: Claudia
authors.initials: C
authors.lastname: Lopes
authors.forename: Hagen
authors.initials: H
authors.lastname: Wende
authors.forename: Zhen
authors.initials: Z
authors.lastname: Guo
authors.forename: Leping
authors.initials: L
authors.lastname: Cheng
authors.forename: Carmen
authors.initials: C
authors.lastname: Birchmeier
authors.forename: Qiufu
authors.initials: Q
authors.lastname: Ma
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002211:Capsaicin / Q000633:toxicity; D002452:Cell Count; D002738:Chloroquine / Q000633:toxicity; D004622:Embryo, Mammalian; D005727:Ganglia, Spinal / Q000166:cytology*; D019886:Gastrin-Releasing Peptide / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology*; D018398:Homeodomain Proteins / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D009124:Muscle Proteins / Q000235:genetics; D009474:Neurons / Q000145:classification* / Q000502:physiology*; D009842:Oligopeptides / Q000633:toxicity; D010146:Pain / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism; D010812:Physical Stimulation / Q000009:adverse effects; D011493:Protein Kinase C / Q000378:metabolism; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism; D011537:Pruritus / Q000209:etiology / Q000378:metabolism; D011597:Psychomotor Performance / Q000187:drug effects / Q000502:physiology; D012677:Sensation / Q000235:genetics*; D013004:Somatostatin / Q000235:genetics / Q000378:metabolism; D015320:Tachykinins / Q000235:genetics / Q000378:metabolism; D050598:Vesicular Glutamate Transport Protein 1 / Q000378:metabolism
chemical_list: D018398:Homeodomain Proteins; C491868:Lbx1h protein, mouse; D009124:Muscle Proteins; D009842:Oligopeptides; D011498:Protein Precursors; C493465:Slc17a7 protein, mouse; D015320:Tachykinins; C487377:Tlx3 protein, mouse; D050598:Vesicular Glutamate Transport Protein 1; C044206:preprotachykinin; C112356:seryl-leucyl-isoleucyl-glycyl--arginyl-leucinamide; D013004:Somatostatin; D019886:Gastrin-Releasing Peptide; D002738:Chloroquine; C087857:protein kinase C gamma; D011493:Protein Kinase C; D002211:Capsaicin
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