title: Wnts are expressed in the spinal cord of adult mice and are differentially induced after injury.
abstract: The Wnt family of proteins plays key roles during central nervous system development and has been involved in several neuropathologies during adulthood, including spinal cord injury (SCI). However, Wnts expression knowledge is relatively limited during adult stages. Here, we sought to define the Wnt family expression pattern after SCI in adult mice by using quantitative polymerase chain reaction (qPCR) and immunohistochemistry (IHC). Under physiological conditions, the messenger RNAs (mRNAs) of most Wnt ligands, inhibitors, receptors, and coreceptors are constitutively expressed in healthy adult mice. After dorsal hemisection, we found significant time-dependent variations, with a prominent up-regulation of Wnt inhibitory factor 1 (Wif1). IHC against Frizzled (Fz) 1 and Fz4, as representatives of late and acute up-regulated receptors, showed a differential expression in the uninjured spinal cord of Fz1 by neurons and oligodendrocytes and Fz4 by astrocytes. After injury, both receptors were maintained in the same type of cells. Finally, by using BATgal reporter mice, our results revealed active β-catenin signaling in neurons of the dorsal horn and cells of the central canal of uninjured spinal cords, besides a lack of additional SCI-induced activation. In conclusion, we demonstrate Wnt expression in the adult spinal cord of mice that is modulated by SCI, which differs from that previously described in rats. Further, Fz receptors are differentially expressed by neurons and glial cells, suggestive for cell-specific patterns and thus diverse physiological roles. Further studies will help toward in-depth characterization of the role of all Wnt factors and receptors described and eventually allow for the design of novel therapies.
authors.affiliation: 1 Molecular Neurology Laboratory, Hospital Nacional de Paraplejicos (HNP) , Toledo, Spain .
authors.forename: Carlos
authors.initials: C
authors.lastname: González-Fernández
authors.forename: Carmen María
authors.initials: CM
authors.lastname: Fernández-Martos
authors.forename: Shannon D
authors.initials: SD
authors.lastname: Shields
authors.forename: Ernest
authors.initials: E
authors.lastname: Arenas
authors.forename: Francisco
authors.initials: F
authors.lastname: Javier Rodríguez
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D005260:Female; D051157:Frizzled Receptors / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000378:metabolism*; D013116:Spinal Cord / Q000378:metabolism*; D013119:Spinal Cord Injuries / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D051157:Frizzled Receptors; D051153:Wnt Proteins