The Transcription Regulator Patz1 Is Essential for Neural Stem Cell Maintenance and Proliferation
Proper regulation of neurogenesis, the process by which new neurons are generated from neural stem and progenitor cells (NS/PCs), is essential for embryonic brain development and adult brain function. The transcription regulator Patz1 is ubiquitously expressed in early mouse embryos and has a key ro...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-04-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2021.657149/full |
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| author | Sara Mancinelli Sara Mancinelli Sara Mancinelli Michela Vitiello Maria Donnini Francesca Mantile Giuseppe Palma Antonio Luciano Claudio Arra Laura Cerchia Giovanna Lucia Liguori Monica Fedele |
| author_facet | Sara Mancinelli Sara Mancinelli Sara Mancinelli Michela Vitiello Maria Donnini Francesca Mantile Giuseppe Palma Antonio Luciano Claudio Arra Laura Cerchia Giovanna Lucia Liguori Monica Fedele |
| author_sort | Sara Mancinelli |
| collection | DOAJ |
| description | Proper regulation of neurogenesis, the process by which new neurons are generated from neural stem and progenitor cells (NS/PCs), is essential for embryonic brain development and adult brain function. The transcription regulator Patz1 is ubiquitously expressed in early mouse embryos and has a key role in embryonic stem cell maintenance. At later stages, the detection of Patz1 expression mainly in the developing brain suggests a specific involvement of Patz1 in neurogenesis. To address this point, we first got insights in Patz1 expression profile in different brain territories at both embryonic and postnatal stages, evidencing a general decreasing trend with respect to time. Then, we performed in vivo and ex vivo analysis of Patz1-knockout mice, focusing on the ventricular and subventricular zone, where we confirmed Patz1 enrichment through the analysis of public RNA-seq datasets. Both embryos and adults showed a significant reduction in the number of Patz1-null NS/PCs, as well as of their self-renewal capability, compared to controls. Consistently, molecular analysis revealed the downregulation of stemness markers in NS/PCs derived from Patz1-null mice. Overall, these data demonstrate the requirement of Patz1 for NS/PC maintenance and proliferation, suggesting new roles for this key transcription factor specifically in brain development and plasticity, with possible implications for neurodegenerative disorders and glial brain tumors. |
| first_indexed | 2024-12-14T02:16:45Z |
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| id | doaj.art-1a9167aee69749cb8ef0c6bdca4a2380 |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-12-14T02:16:45Z |
| publishDate | 2021-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-1a9167aee69749cb8ef0c6bdca4a23802022-12-21T23:20:36ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2021-04-01910.3389/fcell.2021.657149657149The Transcription Regulator Patz1 Is Essential for Neural Stem Cell Maintenance and ProliferationSara Mancinelli0Sara Mancinelli1Sara Mancinelli2Michela Vitiello3Maria Donnini4Francesca Mantile5Giuseppe Palma6Antonio Luciano7Claudio Arra8Laura Cerchia9Giovanna Lucia Liguori10Monica Fedele11Institute of Genetics and Biophysics, National Research Council, Naples, ItalyDepartment of Biomedical Sciences, Humanitas University, Pieve Emanuele, ItalyIstituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Humanitas Research Hospital, Rozzano, ItalyInstitute for Experimental Endocrinology and Oncology, National Research Council, Naples, ItalyInstitute of Genetics and Biophysics, National Research Council, Naples, ItalyInstitute of Genetics and Biophysics, National Research Council, Naples, ItalyStruttura Semplice Dipartimentale (S.S.D.) Sperimentazione Animale, Istituto Nazionale Tumori—Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS)–Fondazione G. Pascale, Naples, ItalyStruttura Semplice Dipartimentale (S.S.D.) Sperimentazione Animale, Istituto Nazionale Tumori—Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS)–Fondazione G. Pascale, Naples, ItalyStruttura Semplice Dipartimentale (S.S.D.) Sperimentazione Animale, Istituto Nazionale Tumori—Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS)–Fondazione G. Pascale, Naples, ItalyInstitute for Experimental Endocrinology and Oncology, National Research Council, Naples, ItalyInstitute of Genetics and Biophysics, National Research Council, Naples, ItalyInstitute for Experimental Endocrinology and Oncology, National Research Council, Naples, ItalyProper regulation of neurogenesis, the process by which new neurons are generated from neural stem and progenitor cells (NS/PCs), is essential for embryonic brain development and adult brain function. The transcription regulator Patz1 is ubiquitously expressed in early mouse embryos and has a key role in embryonic stem cell maintenance. At later stages, the detection of Patz1 expression mainly in the developing brain suggests a specific involvement of Patz1 in neurogenesis. To address this point, we first got insights in Patz1 expression profile in different brain territories at both embryonic and postnatal stages, evidencing a general decreasing trend with respect to time. Then, we performed in vivo and ex vivo analysis of Patz1-knockout mice, focusing on the ventricular and subventricular zone, where we confirmed Patz1 enrichment through the analysis of public RNA-seq datasets. Both embryos and adults showed a significant reduction in the number of Patz1-null NS/PCs, as well as of their self-renewal capability, compared to controls. Consistently, molecular analysis revealed the downregulation of stemness markers in NS/PCs derived from Patz1-null mice. Overall, these data demonstrate the requirement of Patz1 for NS/PC maintenance and proliferation, suggesting new roles for this key transcription factor specifically in brain development and plasticity, with possible implications for neurodegenerative disorders and glial brain tumors.https://www.frontiersin.org/articles/10.3389/fcell.2021.657149/fullneurogenesisneural stem cellsPATZ1knockout miceneurosphere assaysubventricular zone |
| spellingShingle | Sara Mancinelli Sara Mancinelli Sara Mancinelli Michela Vitiello Maria Donnini Francesca Mantile Giuseppe Palma Antonio Luciano Claudio Arra Laura Cerchia Giovanna Lucia Liguori Monica Fedele The Transcription Regulator Patz1 Is Essential for Neural Stem Cell Maintenance and Proliferation Frontiers in Cell and Developmental Biology neurogenesis neural stem cells PATZ1 knockout mice neurosphere assay subventricular zone |
| title | The Transcription Regulator Patz1 Is Essential for Neural Stem Cell Maintenance and Proliferation |
| title_full | The Transcription Regulator Patz1 Is Essential for Neural Stem Cell Maintenance and Proliferation |
| title_fullStr | The Transcription Regulator Patz1 Is Essential for Neural Stem Cell Maintenance and Proliferation |
| title_full_unstemmed | The Transcription Regulator Patz1 Is Essential for Neural Stem Cell Maintenance and Proliferation |
| title_short | The Transcription Regulator Patz1 Is Essential for Neural Stem Cell Maintenance and Proliferation |
| title_sort | transcription regulator patz1 is essential for neural stem cell maintenance and proliferation |
| topic | neurogenesis neural stem cells PATZ1 knockout mice neurosphere assay subventricular zone |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2021.657149/full |
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