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Transmissible spongiform encephalopathies (TSEs), or prion diseases, are neurodegenerative diseases that affect many mammalian species. Some examples include bovine spongiform encephalopathy (BSE) in cattle, scrapie in sheep and goats, Creutzfeldt-Jakob [...]

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ydbio.2007.09.036 Byline: Julie A. Siegenthaler (a), Michael W. Miller (a)(b)(c)(d) Keywords: Cell cycle exit; Cortical hem; Foxg1; Foxo3a; Neurogenesis; p21; p73; Reelin; Septum; Strionuclear neuroepithelium Abbreviations: CKI, cyclin-dependent kinase inhibitor; CR, Cajal-Retzius; Foxg1.sup.Cre/Cre , Foxg1-null; Foxg1.sup.+/+ , wild type; G, gestational day; IGF, insulin-like growth factor; PBS, 0.10 M phosphate-buffered saline; PCNA, proliferating cell nuclear antigen; PI3-K, phosphatidylinositol 3-kinase; pSmad, phosphorylated Smad; SN, strionuclear neuroepithelium; TGF, transforming growth factor; TGF[beta]rI, transforming growth factor [beta] receptor type I; TGF[beta]rII, transforming growth factor [beta] receptor type II; VZ, ventricular zone Abstract: The generation of Cajal-Retzius (CR) neurons is restricted to discrete sites in the telencephalon. Most of these sites do not express Foxg1, a transcription factor that inhibits transforming growth factor (TGF)[beta]-dependent upregulation of p21. We tested the hypothesis that TGF[beta] signaling triggers CR neurogenesis in Foxg1-deficient zones through p21 induction. In Foxg1.sup.+/+ mice, p21 (a) was expressed in select cycling cells in CR neuron-producing areas and (b) was co-localized in newly generated CR neurons. Zones of CR neuronal production and p21 expression were expanded in the forebrains of Foxg1.sup.Cre/Cre mice. Manipulation of TGF[beta] signaling in explants from cortical hems of wild-type mice altered p21 expression and the production of CR neurons. Furthermore, despite continued TGF[beta] activity, p21 immunoreactivity diminished in CR neurons with distance from their generation site. This implicated a second pathway controlling p21 expression. We provide evidence that Foxo3a, which has been shown to translocate into the nucleus to act as a transcriptional co-activator of TGF[beta]-dependent upregulation of p21, is strategically expressed to be involved in controlling p21 expression in CR neurons. Specifically, Foxo3a was nuclear in p21+/reelin+ cells in sites of CR neuronal generation, however, nuclear Foxo3a immunoreactivity was absent in p21-/reelin+ cells distal from sites of CR neurogenesis. Thus, TGF[beta] and Foxo3a may work in concert to regulate expression of p21 during CR neuronal generation. Author Affiliation: (a) Department of Neuroscience and Physiology, State University of New York-Upstate Medical University, Syracuse, NY 13210, USA (b) Developmental Exposure Alcohol Research Center, Binghamton, NY 13902, USA (c) Developmental Exposure Alcohol Research Center, Syracuse, NY 13210, USA (d) Research Service, Veterans Affairs Medical Center, Syracuse, NY 13210, USA Article History: Received 11 May 2007; Revised 18 September 2007; Accepted 19 September 2007

Chronic wasting disease (CWD) of deer and elk is a widespread health concern because its potential for cross-species transmission is undetermined. CWD prevalence in wild elk is much lower than [...]

The transmission of the prion disease bovine spongiform encephalopathy (BSE) to humans raises concern about chronic wasting disease (CWD), a prion disease of deer and elk. In 7 Colorado counties [...]

Whether transmission of the chronic wasting disease (CWD) prion among cervids requires direct interaction with infected animals has been unclear. We report that CWD can be transmitted to susceptible animals [...]

Chronic wasting disease (CWD) of deer and elk is endemic in a tri-corner area of Colorado, Wyoming, and Nebraska, and new foci of CWD have been detected in other parts [...]