1: FASEB J. 2005 Sep;19(11):1537-9. Epub 2005 Jun 21. Serotonergic-like progenitor cells propagated from neural stem cells in vitro: survival with SERT protein expression following implantation into brains of mice lacking SERT. Ren-Patterson RF, Kim DK, Zheng X, Sherrill S, Huang SJ, Tolliver T, Murphy DL. Laboratory of Clinical Science, National Institute of Mental Health, NIH, Bethesda, MD 20892-1264, USA. renpatr@intra.nimh.nih.gov Neural stem cells (NSCs) obtained from the midbrain region of embryonic (E14) mice were initially cultured with basic fibroblast growth factor (bFGF), Sonic hedgehog, and FGF-8 in a serum-free N-2 culture medium to foster differentiation into a serotonergic-like phenotype. During the initial differentiating phase, these progenitor cells expressed En1, Pax3, and Pax5 mRNA. Subsequently, a single serotonin [5-hydroxytryptamine (5-HT)] and tryptophan hydroxylase-positive clone was isolated, which gave rise to cells that developed serotonergic properties. Sixty percent of these progenitor cells expressed the serotonin transporter (SERT), as indicated by specific ligand binding of [125I]-RTI-55. To further evaluate SERT functionality, we showed that these progenitor cells possessed specific [3H]-5-HT uptake activity. Implantation of the serotonergic-like progenitors into the hippocampus of adult mice genetically lacking SERT was followed by migration of these cells into adjacent brain regions, and survival of the cells at 8 weeks was accompanied by a gradual increase in density of SERT protein expression, which was not found in vehicle-injected, control mice. These findings suggest that this serotonergic-like NSC model will be a useful contribution to the development of cell biotechnology in regard to the expression of missing genes such as SERT in the adult brain. PMID: 15972295 [PubMed - in process] --------------------------------------------------------------- 2: Int J Biochem Cell Biol. 1997 Dec;29(12):1449-61. Chromosomal translocations involving paired box transcription factors in human cancer. Barr FG. Department of Pathology, University of Pennslvania School of Medicine, Philadelphia 19104-6082, USA. The PAX genes encode a family of transcription factors that control development within the neural, myogenic, lymphoid, and a variety of other lineages. These proteins are postulated to regulate expression of gene products that function in the control of cellular processes are fundamental to the development of cancer, and thus genetic alterations of these genes may contribute to neoplastic development within these lineages. In support of this premise, several PAX genes have been shown to be targets of consistent chromosomal translocations associated with specific tumor types. The t(2;13) and t(1;13) translocations associated with the myogenic soft tissue cancer alveolar rhabdomyosarcoma fuse portions of the PAX3 or PAX7 gene with a portion of the FKHR gene to generate novel fusion proteins. The t(9;14) translocation associated with the B cell tumor lymphoplasmacytoid lymphoma juxtaposes the PAX5 gene into the vicinity of the IGH locus to deregulate PAX5 expression. This review will examine the molecular basis of these translocations and the role of altered function or expression of paired box transcription factors in the process of tumorigenesis. Publication Types: Review Review, Tutorial PMID: 9570138 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 3: Gene. 1995 Sep 11;162(2):267-70. Identification of DNA recognition sequences for the Pax3 paired domain. Chalepakis G, Gruss P. Max-Planck Institute for Biophysical Chemistry, Gottingen, Germany. The Pax gene family, encoding transcription factors, has been classified into four subfamilies according to their genomic organization, the sequences of the paired domains (PD) and the expression pattern. Pax1 and Pax9 constitute one subfamily, Pax2, Pax5 and Pax8 another, Pax3 and Pax7 another one and Pax4 and Pax6 the fourth subfamily. The PD exhibits DNA-binding activity, and is the most conserved functional motif in all Pax proteins. A high-resolution analysis of a PD structure has been performed [Xu et al., Cell 80 (1995) 639-650] and the DNA-binding characteristics of members of two Pax subfamilies (Pax2, Pax5 and Pax6) have been determined. Here, we have utilized a PCR-based selection approach to identify the DNA-binding sequences of the Pax3/PD, a member of a subfamily which has not yet been characterized. Comparison of the Pax3/PD-binding sequences with those of other PD proteins revealed both similarities and differences in the DNA-recognition sequence. This suggests that different Pax proteins can regulate the expression of the same target gene, but they can also regulate the expression of completely unrelated genes by binding to their DNA regulatory regions. PMID: 7557441 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 4: C R Acad Sci III. 1995 Jan;318(1):57-66. PAX-genes expression during human embryonic development, a preliminary report. Gerard M, Abitbol M, Delezoide AL, Dufier JL, Mallet J, Vekemans M. Laboratoire d'histologie-embryologie-cytogenetique, Universite Rene-Descartes (Paris-V), Faculte de medecine Necker, France. PAX-genes encode important transcriptional factors during embryogenesis. They are also involved in human diseases, Waardenburg syndrome, Aniridia and tumors. We report in the present paper a preliminary in situ hybridization study of PAX3-, PAX5- and PAX6-gene expression during human embryonic development. PAX3-gene is expressed in the neural groove before closure, and in the closed neural tube. Afterwards, its expression is observed in the mesencephalon, the rhombencephalon and the spinal cord. PAX5-gene expression is restricted to the mesencephalon-rhombencephalon boundary and the spinal cord. PAX6-gene is expressed early in the neural tube, just after its closure. Afterwards, its expression is observed in the forebrain, the rhombencephalon, the somites and the spinal cord. These patterns of expression are observed early during human embryonic development and are specific in time and space. This preliminary report shows the feasibility of in situ hybridization methodology for studying the expression of developmental genes during the early stages of human embryogenesis. It opens the way to study the pathogenesis of polymalformative syndromes and tumorigenesis. PMID: 7757805 [PubMed - indexed for MEDLINE] ---------------------------------------------------------------