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Light mechanical stimulation of hairy skin can induce a form of itch known as mechanical itch. This itch sensation is normally suppressed by inputs from mechanoreceptors; however, in many forms of chronic itch, including alloknesis, this gating mechanism is lost. Here we demonstrate that a population of spinal inhibitory interneurons that are defined by the expression of neuropeptide Y::Cre (NPY::Cre) act to gate mechanical itch. Mice in which dorsal NPY::Cre-derived neurons are selectively ablated or silenced develop mechanical itch without an increase in sensitivity to chemical itch or pain. This chronic itch state is histamine-independent and is transmitted independently of neurons that express the gastrin-releasing peptide receptor. Thus, our studies reveal a dedicated spinal cord inhibitory pathway that gates the transmission of mechanical itch.

Author(s): Simon Gosgnach [1, 6]; Guillermo M. Lanuza [1, 6]; Simon J. B. Butt [3, 5]; Harald Saueressig [1]; Ying Zhang [1]; Tomoko Velasquez [1]; Dieter Riethmacher [4]; Edward M. [...]

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ydbio.2005.12.010 Byline: Eiko Nakahira (a), Tetsushi Kagawa (a)(b)(c), Takeshi Shimizu (c), Martyn D. Goulding (d), Kazuhiro Ikenaka (a) Keywords: Oligodendrocyte; Forebrain; Migration; In utero electroporation; Olig2; PDGFR[alpha] Abstract: Cortical neuroepithelial cells generate neurons, astrocytes, and oligodendrocytes (OLs) in vitro. However, whether cortical OLs are derived from the cortical neuroepithelium or migrate from the ventral forebrain is under severe debate yet. This is due to the fact that OL progenitor cells (OPCs), as marked by the expression of PDGFR[alpha] or NG2, are generated at around embryonic day (E) 11 or 12 in the mouse ganglionic eminences, but the myelinating OLs appear during the second week postnatally in the cortex. There has been no labeling method for long-term glial cell-lineage tracing. Thus, we developed a new strategy: plasmid DNA encoding Cre recombinase was introduced into the Cre/loxP reporter forebrain in ventral- or dorsal-specific manner by in utero DNA electroporation. The reporter gfp gene is expressed permanently owing to the chromosomal DNA recombination. The GFP-labeled myelinating OLs were detected in the adult cortex when electroporation was targeted to the ventral neuroepithelium, demonstrating at least some of the myelinating OLs are derived from the ventral forebrain. However, when electroporation was targeted to the dorsal, we could not find GFP-labeled myelinating OLs. This suggests that the progenitors of cortical OPCs are absent or located at restricted regions in the dorsal forebrain (cortex) at E12. Author Affiliation: (a) Laboratory of Neurobiology and Bioinformatics, National Institute for Physiological Sciences, 5-1 Higashiyama, Myodaiji, Okazaki 444-8787, Japan (b) Laboratory of Active Transport, National Institute for Physiological Sciences, 5-1 Higashiyama, Myodaiji, Okazaki 444-8787, Japan (c) Division of Cell Fate Modulation, Institute of Molecular Embryology and Genetics, Kumamoto University, 2-2-1 Honjo, Kumamoto, Kumamoto 860-0811, Japan (d) Molecular Neurobiology Goulding Lab, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92186-5800, USA Article History: Received 22 June 2005; Revised 29 November 2005; Accepted 5 December 2005

Immunohistochemistry and polymerase chain reaction were performed on specimens obtained from chick embryonic tissues to study the genetic regulation of myogenesis. The results showed that either signals from the overlying ectoderm or Wnt and Sonic hedgehog signals can induce somitic expression of the paired box transcription factors, Pax-3 and Pax-7, concomitant with the expression of Myf-5 and prior to that of MyoD. The findings also identified the retrovirus gene product Pax-3 as a key regulator of somitic myogenesis.

During nephrogenesls, dynamic changes in the expression of cell adhesion molecules are evident as epithelial structures differentiate from the induced mesenchyme. The cadherins are thought to play an important role in the metanephric mesenchyme, when cells aggregate to form the renal vesicle, a polarized epithelial structure which eventually fuses with the ureteric bud to generate a continuous nascent nephron. We have generated and analyzed mice with a targeted mutation in the gene encoding cadherin-6 (Cad-6), a type II cadherin expressed during early stages of nephrogenesis. These mice are viable and fertile, and they complete both early and late aspects of nephrogenesis. However, upon closer examination in vitro and in vivo, a fraction of the induced metanephric mesenchyme in Cad-6 mutant kidneys fails to form a fully polarized epithelium on schedule. Moreover, a significant number of the renal vesicles in Cad-6 mutant kidneys apparently fail to fuse to the ureteric bud. These alterations in epithelialization and fusion apparently lead to a loss of nephrons in the adult. These studies support the idea that cadherins play an essential role in the formation of epithelial structures and underscore the importance of timing in orchestrating the morphogenesis of complex epithelial tissues. Key Words: cadherin-6; kidney development; epithelial polarization; epithelium fusion; renal tubules.