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Nolz1 promotes striatal neurogenesis through the regulation of retinoic acid signaling

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dc.creator Urbán Avellaneda, Noelia
dc.creator Martín Ibáñez, Raquel
dc.creator Herranz, Cristina
dc.creator Esgleas, Miriam
dc.creator Crespo, Empar
dc.creator Pardo Muñoz, Mònica
dc.creator Crespo-Enríquez, Ivan
dc.creator Méndez-Gómez, Héctor R.
dc.creator Waclaw, Ronald
dc.creator Chatzi, Christina
dc.creator Álvarez, Susana
dc.creator Álvarez, Rosana
dc.creator Duester, Gregg
dc.creator Campbell, Kenneth
dc.creator Lera, Ángel R. de
dc.creator Vicario Abejón, Carlos
dc.creator Martínez, Salvador
dc.creator Alberch i Vié, Jordi, 1959-
dc.creator Canals i Coll, Josep M.
dc.date 2010-09-21T12:34:50Z
dc.date 2010-09-21T12:34:50Z
dc.date 2010
dc.date.accessioned 2024-12-16T10:25:17Z
dc.date.available 2024-12-16T10:25:17Z
dc.identifier 1749-8104
dc.identifier http://hdl.handle.net/2445/13753
dc.identifier 582600
dc.identifier 20735826
dc.identifier.uri http://fima-docencia.ub.edu:8080/xmlui/handle/123456789/19146
dc.description Background: Nolz1 is a zinc finger transcription factor whose expression is enriched in the lateral ganglionic eminence (LGE), although its function is still unknown. Results: Here we analyze the role of Nolz1 during LGE development. We show that Nolz1 expression is high in proliferating neural progenitor cells (NPCs) of the LGE subventricular zone. In addition, low levels of Nolz1 are detected in the mantle zone, as well as in the adult striatum. Similarly, Nolz1 is highly expressed in proliferating LGE-derived NPC cultures, but its levels rapidly decrease upon cell differentiation, pointing to a role of Nolz1 in the control of NPC proliferation and/or differentiation. In agreement with this hypothesis, we find that Nolz1 over-expression promotes cell cycle exit of NPCs in neurosphere cultures and negatively regulates proliferation in telencephalic organotypic cultures. Within LGE primary cultures, Nolz1 over-expression promotes the acquisition of a neuronal phenotype, since it increases the number of β-III tubulin (Tuj1)- and microtubule-associated protein (MAP)2-positive neurons, and inhibits astrocyte generation and/or differentiation. Retinoic acid (RA) is one of the most important morphogens involved in striatal neurogenesis, and regulates Nolz1 expression in different systems. Here we show that Nolz1 also responds to this morphogen in E12.5 LGE-derived cell cultures. However, Nolz1 expression is not regulated by RA in E14.5 LGE-derived cell cultures, nor is it affected during LGE development in mouse models that present decreased RA levels. Interestingly, we find that Gsx2, which is necessary for normal RA signaling during LGE development, is also required for Nolz1 expression, which is lost in Gsx2 knockout mice. These findings suggest that Nolz1 might act downstream of Gsx2 to regulate RA-induced neurogenesis. Keeping with this hypothesis, we show that Nolz1 induces the selective expression of the RA receptor (RAR)β without altering RARα or RARγ. In addition, Nozl1 over-expression increases RA signaling since it stimulates the RA response element. This RA signaling is essential for Nolz1-induced neurogenesis, which is impaired in a RA-free environment or in the presence of a RAR inverse agonist. It has been proposed that Drosophila Gsx2 and Nolz1 homologues could cooperate with the transcriptional co-repressors Groucho-TLE to regulate cell proliferation. In agreement with this view, we show that Nolz1 could act in collaboration with TLE-4, as they are expressed at the same time in NPC cultures and during mouse development. Conclusions: Nolz1 promotes RA signaling in the LGE, contributing to the striatal neurogenesis during development.
dc.format 22 p.
dc.format application/pdf
dc.language eng
dc.publisher BioMed Central
dc.relation Reproducció del document publicat a http://dx.doi.org/10.1186/1749-8104-5-21
dc.relation Neural Development 2010, 5:21
dc.relation http://dx.doi.org/10.1186/1749-8104-5-21
dc.rights cc-by (c) Urban et al., 2010
dc.rights http://creativecommons.org/licenses/by/2.0
dc.rights info:eu-repo/semantics/openAccess
dc.source Articles publicats en revistes (Biomedicina)
dc.subject Neurobiologia del desenvolupament
dc.subject Embriologia
dc.subject Developmental neurobiology
dc.subject Embryology
dc.title Nolz1 promotes striatal neurogenesis through the regulation of retinoic acid signaling
dc.type info:eu-repo/semantics/article
dc.type info:eu-repo/semantics/publishedVersion


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