The transcription factor Sox2 is essential for neural stem cells (NSC) maintenance in the hippocampus and in vitro. The transcription factor Emx2 is also critical for hippocampal development and NSC self-renewal. Searching for 'modifier' genes affecting the Sox2 deficiency phenotype in mouse, we observed that loss of one Emx2 allele substantially increased the telencephalic β-geo (LacZ) expression of a transgene driven by the 5' or 3' Sox2 enhancer. Reciprocally, Emx2 overexpression in NSC cultures inhibited the activity of the same transgene. In vivo, loss of one Emx2 allele increased Sox2 levels in the medial telencephalic wall, including the hippocampal primordium. In hypomorphic Sox2 mutants, retaining a single 'weak' Sox2 allele, Emx2 deficiency substantially rescued hippocampal radial glia stem cells and neurogenesis, indicating that Emx2 functionally interacts with Sox2 at the stem cell level. Electrophoresis mobility shift assays and transfection indicated that Emx2 represses the activities of both Sox2 enhancers. Emx2 bound to overlapping Emx2/POU-binding sites, preventing binding of the POU transcriptional activator Brn2. Additionally, Emx2 directly interacted with Brn2 without binding to DNA. These data imply that Emx2 may perform part of its functions by negatively modulating Sox2 in specific brain areas, thus controlling important aspects of NSC function in development.

Emx2 is a dose-dependent negative regulator of Sox2 telencephalic enhancers / Mariani, J; Favaro, R; Lancini, C; Vaccari, G; Ferri, Al; Bertolini, J; Tonoli, D; Latorre, E; Caccia, R; Ronchi, A; Ottolenghi, S; Miyagi, S; Okuda, A; Zappavigna, Vincenzo; Nicolis, Sk. - In: NUCLEIC ACIDS RESEARCH. - ISSN 0305-1048. - STAMPA. - 40:14(2012), pp. 6461-6476. [10.1093/nar/gks295]

Emx2 is a dose-dependent negative regulator of Sox2 telencephalic enhancers.

ZAPPAVIGNA, Vincenzo;
2012

Abstract

The transcription factor Sox2 is essential for neural stem cells (NSC) maintenance in the hippocampus and in vitro. The transcription factor Emx2 is also critical for hippocampal development and NSC self-renewal. Searching for 'modifier' genes affecting the Sox2 deficiency phenotype in mouse, we observed that loss of one Emx2 allele substantially increased the telencephalic β-geo (LacZ) expression of a transgene driven by the 5' or 3' Sox2 enhancer. Reciprocally, Emx2 overexpression in NSC cultures inhibited the activity of the same transgene. In vivo, loss of one Emx2 allele increased Sox2 levels in the medial telencephalic wall, including the hippocampal primordium. In hypomorphic Sox2 mutants, retaining a single 'weak' Sox2 allele, Emx2 deficiency substantially rescued hippocampal radial glia stem cells and neurogenesis, indicating that Emx2 functionally interacts with Sox2 at the stem cell level. Electrophoresis mobility shift assays and transfection indicated that Emx2 represses the activities of both Sox2 enhancers. Emx2 bound to overlapping Emx2/POU-binding sites, preventing binding of the POU transcriptional activator Brn2. Additionally, Emx2 directly interacted with Brn2 without binding to DNA. These data imply that Emx2 may perform part of its functions by negatively modulating Sox2 in specific brain areas, thus controlling important aspects of NSC function in development.
2012
40
14
6461
6476
Emx2 is a dose-dependent negative regulator of Sox2 telencephalic enhancers / Mariani, J; Favaro, R; Lancini, C; Vaccari, G; Ferri, Al; Bertolini, J; Tonoli, D; Latorre, E; Caccia, R; Ronchi, A; Ottolenghi, S; Miyagi, S; Okuda, A; Zappavigna, Vincenzo; Nicolis, Sk. - In: NUCLEIC ACIDS RESEARCH. - ISSN 0305-1048. - STAMPA. - 40:14(2012), pp. 6461-6476. [10.1093/nar/gks295]
Mariani, J; Favaro, R; Lancini, C; Vaccari, G; Ferri, Al; Bertolini, J; Tonoli, D; Latorre, E; Caccia, R; Ronchi, A; Ottolenghi, S; Miyagi, S; Okuda, ...espandi
File in questo prodotto:
File Dimensione Formato  
gks295.pdf

Open access

Descrizione: Articolo principale
Tipologia: Versione pubblicata dall'editore
Dimensione 14.46 MB
Formato Adobe PDF
14.46 MB Adobe PDF Visualizza/Apri
Pubblicazioni consigliate

Licenza Creative Commons
I metadati presenti in IRIS UNIMORE sono rilasciati con licenza Creative Commons CC0 1.0 Universal, mentre i file delle pubblicazioni sono rilasciati con licenza Attribuzione 4.0 Internazionale (CC BY 4.0), salvo diversa indicazione.
In caso di violazione di copyright, contattare Supporto Iris

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/913890
Citazioni
  • ???jsp.display-item.citation.pmc??? 17
  • Scopus 22
  • ???jsp.display-item.citation.isi??? 20
social impact