<it>Nolz1 </it>promotes striatal neurogenesis through the regulation of retinoic acid signaling
<p>Abstract</p> <p>Background</p> <p><it>Nolz1 </it>is a zinc finger transcription factor whose expression is enriched in the lateral ganglionic eminence (LGE), although its function is still unknown.</p> <p>Results</p> <p>Here we ana...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2010-08-01
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| Series: | Neural Development |
| Online Access: | http://www.neuraldevelopment.com/content/5/1/21 |
| _version_ | 1819086036062437376 |
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| author | Urbán Noelia Martín-Ibáñez Raquel Herranz Cristina Esgleas Miriam Crespo Empar Pardo Monica Crespo-Enríquez Ivan Méndez-Gómez Héctor R Waclaw Ronald Chatzi Christina Álvarez Susana Álvarez Rosana Duester Gregg Campbell Kenneth de Lera Angel R Vicario-Abejón Carlos Martinez Salvador Alberch Jordi Canals Josep M |
| author_facet | Urbán Noelia Martín-Ibáñez Raquel Herranz Cristina Esgleas Miriam Crespo Empar Pardo Monica Crespo-Enríquez Ivan Méndez-Gómez Héctor R Waclaw Ronald Chatzi Christina Álvarez Susana Álvarez Rosana Duester Gregg Campbell Kenneth de Lera Angel R Vicario-Abejón Carlos Martinez Salvador Alberch Jordi Canals Josep M |
| author_sort | Urbán Noelia |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p><it>Nolz1 </it>is a zinc finger transcription factor whose expression is enriched in the lateral ganglionic eminence (LGE), although its function is still unknown.</p> <p>Results</p> <p>Here we analyze the role of <it>Nolz1 </it>during LGE development. We show that <it>Nolz1 </it>expression is high in proliferating neural progenitor cells (NPCs) of the LGE subventricular zone. In addition, low levels of <it>Nolz1 </it>are detected in the mantle zone, as well as in the adult striatum. Similarly, <it>Nolz1 </it>is highly expressed in proliferating LGE-derived NPC cultures, but its levels rapidly decrease upon cell differentiation, pointing to a role of <it>Nolz1 </it>in the control of NPC proliferation and/or differentiation. In agreement with this hypothesis, we find that <it>Nolz1 </it>over-expression promotes cell cycle exit of NPCs in neurosphere cultures and negatively regulates proliferation in telencephalic organotypic cultures. Within LGE primary cultures, <it>Nolz1 </it>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 <it>Nolz1 </it>expression in different systems. Here we show that <it>Nolz1 </it>also responds to this morphogen in E12.5 LGE-derived cell cultures. However, <it>Nolz1 </it>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 <it>Gsx2</it>, which is necessary for normal RA signaling during LGE development, is also required for <it>Nolz1 </it>expression, which is lost in <it>Gsx2 </it>knockout mice. These findings suggest that <it>Nolz1 </it>might act downstream of <it>Gsx2 </it>to regulate RA-induced neurogenesis. Keeping with this hypothesis, we show that <it>Nolz1 </it>induces the selective expression of the RA receptor (RAR)β without altering RARα or RARγ. In addition, <it>Nozl1 </it>over-expression increases RA signaling since it stimulates the RA response element. This RA signaling is essential for <it>Nolz1</it>-induced neurogenesis, which is impaired in a RA-free environment or in the presence of a RAR inverse agonist. It has been proposed that <it>Drosophila Gsx2 </it>and <it>Nolz1 </it>homologues could cooperate with the transcriptional co-repressors Groucho-TLE to regulate cell proliferation. In agreement with this view, we show that <it>Nolz1 </it>could act in collaboration with TLE-4, as they are expressed at the same time in NPC cultures and during mouse development.</p> <p>Conclusions</p> <p><it>Nolz1 </it>promotes RA signaling in the LGE, contributing to the striatal neurogenesis during development.</p> |
| first_indexed | 2024-12-21T21:13:51Z |
| format | Article |
| id | doaj.art-b26ae718bcc54bc1bce73f169fe09223 |
| institution | Directory Open Access Journal |
| issn | 1749-8104 |
| language | English |
| last_indexed | 2024-12-21T21:13:51Z |
| publishDate | 2010-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Neural Development |
| spelling | doaj.art-b26ae718bcc54bc1bce73f169fe092232022-12-21T18:50:03ZengBMCNeural Development1749-81042010-08-01512110.1186/1749-8104-5-21<it>Nolz1 </it>promotes striatal neurogenesis through the regulation of retinoic acid signalingUrbán NoeliaMartín-Ibáñez RaquelHerranz CristinaEsgleas MiriamCrespo EmparPardo MonicaCrespo-Enríquez IvanMéndez-Gómez Héctor RWaclaw RonaldChatzi ChristinaÁlvarez SusanaÁlvarez RosanaDuester GreggCampbell Kennethde Lera Angel RVicario-Abejón CarlosMartinez SalvadorAlberch JordiCanals Josep M<p>Abstract</p> <p>Background</p> <p><it>Nolz1 </it>is a zinc finger transcription factor whose expression is enriched in the lateral ganglionic eminence (LGE), although its function is still unknown.</p> <p>Results</p> <p>Here we analyze the role of <it>Nolz1 </it>during LGE development. We show that <it>Nolz1 </it>expression is high in proliferating neural progenitor cells (NPCs) of the LGE subventricular zone. In addition, low levels of <it>Nolz1 </it>are detected in the mantle zone, as well as in the adult striatum. Similarly, <it>Nolz1 </it>is highly expressed in proliferating LGE-derived NPC cultures, but its levels rapidly decrease upon cell differentiation, pointing to a role of <it>Nolz1 </it>in the control of NPC proliferation and/or differentiation. In agreement with this hypothesis, we find that <it>Nolz1 </it>over-expression promotes cell cycle exit of NPCs in neurosphere cultures and negatively regulates proliferation in telencephalic organotypic cultures. Within LGE primary cultures, <it>Nolz1 </it>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 <it>Nolz1 </it>expression in different systems. Here we show that <it>Nolz1 </it>also responds to this morphogen in E12.5 LGE-derived cell cultures. However, <it>Nolz1 </it>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 <it>Gsx2</it>, which is necessary for normal RA signaling during LGE development, is also required for <it>Nolz1 </it>expression, which is lost in <it>Gsx2 </it>knockout mice. These findings suggest that <it>Nolz1 </it>might act downstream of <it>Gsx2 </it>to regulate RA-induced neurogenesis. Keeping with this hypothesis, we show that <it>Nolz1 </it>induces the selective expression of the RA receptor (RAR)β without altering RARα or RARγ. In addition, <it>Nozl1 </it>over-expression increases RA signaling since it stimulates the RA response element. This RA signaling is essential for <it>Nolz1</it>-induced neurogenesis, which is impaired in a RA-free environment or in the presence of a RAR inverse agonist. It has been proposed that <it>Drosophila Gsx2 </it>and <it>Nolz1 </it>homologues could cooperate with the transcriptional co-repressors Groucho-TLE to regulate cell proliferation. In agreement with this view, we show that <it>Nolz1 </it>could act in collaboration with TLE-4, as they are expressed at the same time in NPC cultures and during mouse development.</p> <p>Conclusions</p> <p><it>Nolz1 </it>promotes RA signaling in the LGE, contributing to the striatal neurogenesis during development.</p>http://www.neuraldevelopment.com/content/5/1/21 |
| spellingShingle | Urbán Noelia Martín-Ibáñez Raquel Herranz Cristina Esgleas Miriam Crespo Empar Pardo Monica Crespo-Enríquez Ivan Méndez-Gómez Héctor R Waclaw Ronald Chatzi Christina Álvarez Susana Álvarez Rosana Duester Gregg Campbell Kenneth de Lera Angel R Vicario-Abejón Carlos Martinez Salvador Alberch Jordi Canals Josep M <it>Nolz1 </it>promotes striatal neurogenesis through the regulation of retinoic acid signaling Neural Development |
| title | <it>Nolz1 </it>promotes striatal neurogenesis through the regulation of retinoic acid signaling |
| title_full | <it>Nolz1 </it>promotes striatal neurogenesis through the regulation of retinoic acid signaling |
| title_fullStr | <it>Nolz1 </it>promotes striatal neurogenesis through the regulation of retinoic acid signaling |
| title_full_unstemmed | <it>Nolz1 </it>promotes striatal neurogenesis through the regulation of retinoic acid signaling |
| title_short | <it>Nolz1 </it>promotes striatal neurogenesis through the regulation of retinoic acid signaling |
| title_sort | it nolz1 it promotes striatal neurogenesis through the regulation of retinoic acid signaling |
| url | http://www.neuraldevelopment.com/content/5/1/21 |
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