title: Genes expressed in mouse cortical progenitors are enriched in Pax, Lhx, and Sox transcription factor putative binding sites.
abstract: Considerable progress has been made in the understanding of molecular and cellular mechanisms controlling the development of the mammalian cortex. The proliferative and neurogenic properties of cortical progenitors located in the ventricular germinal zone start being understood. Little is known however on the cis-regulatory control that finely tunes gene expression in these progenitors. Here, we undertook an in silico-based approach to address this question, followed by some functional validation. Using the Eurexpress database, we established a list of 30 genes specifically expressed in the cortical germinal zone, we selected mouse/human conserved non-coding elements (CNEs) around these genes and we performed motif-enrichment search in these CNEs. We found an over-representation of motifs corresponding to binding sites for Pax, Sox, and Lhx transcription factors, often found as pairs and located within 100bp windows. A small subset of CNEs (n=7) was tested for enhancer activity, by ex-vivo and in utero electroporation assays. Two showed strong enhancer activity in the germinal zone progenitors. Mutagenesis experiments on a selected CNE showed the functional importance of the Pax, Sox, and Lhx TFBS for conferring enhancer activity to the CNE. Overall, from a cis-regulatory viewpoint, our data suggest an input from Pax, Sox and Lhx transcription factors to orchestrate corticogenesis. These results are discussed with regards to the known functional roles of Pax6, Sox2 and Lhx2 in cortical development.
authors.affiliation: DECA Group, Institut des Neurosciences Paris-Saclay, Université Paris-Saclay, Université Paris-Sud, CNRS, UMR 9197, 91198 Gif-sur-Yvette, France. Electronic address: amandine.bery@cea.fr.
authors.forename: Amandine
authors.initials: A
authors.lastname: Bery
authors.affiliation: DECA Group, Institut des Neurosciences Paris-Saclay, Université Paris-Saclay, Université Paris-Sud, CNRS, UMR 9197, 91198 Gif-sur-Yvette, France.
authors.forename: Yohann
authors.initials: Y
authors.lastname: Mérot
authors.affiliation: DECA Group, Institut des Neurosciences Paris-Saclay, Université Paris-Saclay, Université Paris-Sud, CNRS, UMR 9197, 91198 Gif-sur-Yvette, France. Electronic address: retaux@inaf.cnrs-gif.fr.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Rétaux
mesh_terms: D000818:Animals; D001665:Binding Sites; D002540:Cerebral Cortex / Q000502:physiology*; D017124:Conserved Sequence; D018274:Electroporation; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D060850:LIM-Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D016297:Mutagenesis, Site-Directed; D058953:Neural Stem Cells / Q000502:physiology*; D055495:Neurogenesis / Q000502:physiology*; D009924:Organ Culture Techniques; D051761:Paired Box Transcription Factors / Q000235:genetics / Q000378:metabolism; D055747:SOX Transcription Factors / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D059467:Transcriptome
chemical_list: C489783:LHX2 protein, human; D060850:LIM-Homeodomain Proteins; C489784:Lhx2 protein, mouse; D051761:Paired Box Transcription Factors; D055747:SOX Transcription Factors; D014157:Transcription Factors
keywords: Enhancer activity; Lhx2; Motif search; Mutagenesis; Non-coding regulatory element; in vivo electroporation