title: A cis-element in the Notch1 locus is involved in the regulation of gene expression in interneuron progenitors.
abstract: Interneurons comprise approximately one third of the total cortical neurons in the mammalian cerebral cortex. Studies have revealed many details in the generation of this cell type. However, the mechanism that defines interneuron-lineage specific gene expression is not well understood. Gene regulatory elements, e.g., promoters, enhancers, and trans-acting factors, are essential for the proper control of gene expression. Here, we report that a novel evolutionarily conserved cis-element in the second intron of the Notch1 locus plays an important role in regulating gene expression in interneuron progenitors. The spatiotemporal activity of the cis-element in the developing central nervous system (CNS) was determined by both transient reporter expression in the developing chick and a transgenic mouse model. Its activity is well correlated with neurogenesis in both the chick and mouse and restricted to neural progenitor cells in the ganglionic eminence that are fated to differentiate into GABAergic interneurons of the neocortex. We further demonstrate that the cis-element activity requires the binding motif for trans-acting factors Gsh1/Barx2/Brn3. Deletion of this binding motif abolishes reporter gene expression. Together, these data provide new insights into the regulatory mechanisms of interneuron development in the vertebrate CNS.
authors.affiliation: Department of Biomedical Engineering, Rutgers University, 599 Taylor Road, Piscataway, NJ 08854, USA.
authors.forename: Evangeline
authors.initials: E
authors.lastname: Tzatzalos
authors.forename: Shannon M
authors.initials: SM
authors.lastname: Smith
authors.forename: Sung Tae
authors.initials: ST
authors.lastname: Doh
authors.forename: Hailing
authors.initials: H
authors.lastname: Hao
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.forename: Alson
authors.initials: A
authors.lastname: Wu
authors.forename: Martin
authors.initials: M
authors.lastname: Grumet
authors.forename: Li
authors.initials: L
authors.lastname: Cai
mesh_terms: D000818:Animals; D030161:Avian Proteins / Q000235:genetics / Q000378:metabolism; D002465:Cell Movement; D002642:Chick Embryo; D002645:Chickens; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D004742:Enhancer Elements, Genetic; D018507:Gene Expression Regulation, Developmental; D056426:Genetic Loci; D007395:Interneurons / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism*; D011485:Protein Binding; D051881:Receptor, Notch1 / Q000235:genetics* / Q000378:metabolism
chemical_list: D030161:Avian Proteins; C497762:Notch1 protein, mouse; D051881:Receptor, Notch1