Microcephaly Gene Links Trithorax and REST/NRSF to Control Neural Stem Cell Proliferation and Differentiation
Microcephaly is a neurodevelopmental disorder causing significantly reduced cerebral cortex size. Many known microcephaly gene products localize to centrosomes, regulating cell fate and proliferation. Here, we identify and characterize a nuclear zinc finger protein, ZNF335/NIF-1, as a causative gene...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
| Published: |
Elsevier
2014
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| Online Access: | http://hdl.handle.net/1721.1/91519 |
| _version_ | 1826203791287910400 |
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| author | Baltus, Andrew E. Mathew, Rebecca S. Murphy, Elisabeth A. Evrony, Gilad D. Gonzalez, Dilenny M. Wang, Estee P. Marshall-Walker, Christine A. Barry, Brenda J. Murn, Jernej Tatarakis, Antonis Mahajan, Muktar A. Samuels, Herbert H. Shi, Yang Golden, Jeffrey A. Mahajnah, Muhammad Shenhav, Ruthie Walsh, Christopher A. Yang, Yawei |
| author2 | Harvard University--MIT Division of Health Sciences and Technology |
| author_facet | Harvard University--MIT Division of Health Sciences and Technology Baltus, Andrew E. Mathew, Rebecca S. Murphy, Elisabeth A. Evrony, Gilad D. Gonzalez, Dilenny M. Wang, Estee P. Marshall-Walker, Christine A. Barry, Brenda J. Murn, Jernej Tatarakis, Antonis Mahajan, Muktar A. Samuels, Herbert H. Shi, Yang Golden, Jeffrey A. Mahajnah, Muhammad Shenhav, Ruthie Walsh, Christopher A. Yang, Yawei |
| author_sort | Baltus, Andrew E. |
| collection | MIT |
| description | Microcephaly is a neurodevelopmental disorder causing significantly reduced cerebral cortex size. Many known microcephaly gene products localize to centrosomes, regulating cell fate and proliferation. Here, we identify and characterize a nuclear zinc finger protein, ZNF335/NIF-1, as a causative gene for severe microcephaly, small somatic size, and neonatal death. Znf335 null mice are embryonically lethal, and conditional knockout leads to severely reduced cortical size. RNA-interference and postmortem human studies show that ZNF335 is essential for neural progenitor self-renewal, neurogenesis, and neuronal differentiation. ZNF335 is a component of a vertebrate-specific, trithorax H3K4-methylation complex, directly regulating REST/NRSF, a master regulator of neural gene expression and cell fate, as well as other essential neural-specific genes. Our results reveal ZNF335 as an essential link between H3K4 complexes and REST/NRSF and provide the first direct genetic evidence that this pathway regulates human neurogenesis and neuronal differentiation. |
| first_indexed | 2024-09-23T12:43:05Z |
| format | Article |
| id | mit-1721.1/91519 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T12:43:05Z |
| publishDate | 2014 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | mit-1721.1/915192022-09-28T09:37:19Z Microcephaly Gene Links Trithorax and REST/NRSF to Control Neural Stem Cell Proliferation and Differentiation Baltus, Andrew E. Mathew, Rebecca S. Murphy, Elisabeth A. Evrony, Gilad D. Gonzalez, Dilenny M. Wang, Estee P. Marshall-Walker, Christine A. Barry, Brenda J. Murn, Jernej Tatarakis, Antonis Mahajan, Muktar A. Samuels, Herbert H. Shi, Yang Golden, Jeffrey A. Mahajnah, Muhammad Shenhav, Ruthie Walsh, Christopher A. Yang, Yawei Harvard University--MIT Division of Health Sciences and Technology Yang, Yawei Microcephaly is a neurodevelopmental disorder causing significantly reduced cerebral cortex size. Many known microcephaly gene products localize to centrosomes, regulating cell fate and proliferation. Here, we identify and characterize a nuclear zinc finger protein, ZNF335/NIF-1, as a causative gene for severe microcephaly, small somatic size, and neonatal death. Znf335 null mice are embryonically lethal, and conditional knockout leads to severely reduced cortical size. RNA-interference and postmortem human studies show that ZNF335 is essential for neural progenitor self-renewal, neurogenesis, and neuronal differentiation. ZNF335 is a component of a vertebrate-specific, trithorax H3K4-methylation complex, directly regulating REST/NRSF, a master regulator of neural gene expression and cell fate, as well as other essential neural-specific genes. Our results reveal ZNF335 as an essential link between H3K4 complexes and REST/NRSF and provide the first direct genetic evidence that this pathway regulates human neurogenesis and neuronal differentiation. Stuart H.Q. and Victoria Quan Fellowship Fund in Neurobiology (Fellowship) National Institutes of Health (U.S.). Medical Scientist Training Program (Grant T32GM007753) 2014-11-12T13:11:59Z 2014-11-12T13:11:59Z 2012-11 2012-07 Article http://purl.org/eprint/type/JournalArticle 00928674 1097-4172 http://hdl.handle.net/1721.1/91519 Yang, Yawei J., Andrew E. Baltus, Rebecca S. Mathew, Elisabeth A. Murphy, Gilad D. Evrony, Dilenny M. Gonzalez, Estee P. Wang, et al. “Microcephaly Gene Links Trithorax and REST/NRSF to Control Neural Stem Cell Proliferation and Differentiation.” Cell 151, no. 5 (November 2012): 1097–1112. © 2012 Elsevier Inc. en_US http://dx.doi.org/10.1016/j.cell.2012.10.043 Cell Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf Elsevier Elsevier |
| spellingShingle | Baltus, Andrew E. Mathew, Rebecca S. Murphy, Elisabeth A. Evrony, Gilad D. Gonzalez, Dilenny M. Wang, Estee P. Marshall-Walker, Christine A. Barry, Brenda J. Murn, Jernej Tatarakis, Antonis Mahajan, Muktar A. Samuels, Herbert H. Shi, Yang Golden, Jeffrey A. Mahajnah, Muhammad Shenhav, Ruthie Walsh, Christopher A. Yang, Yawei Microcephaly Gene Links Trithorax and REST/NRSF to Control Neural Stem Cell Proliferation and Differentiation |
| title | Microcephaly Gene Links Trithorax and REST/NRSF to Control Neural Stem Cell Proliferation and Differentiation |
| title_full | Microcephaly Gene Links Trithorax and REST/NRSF to Control Neural Stem Cell Proliferation and Differentiation |
| title_fullStr | Microcephaly Gene Links Trithorax and REST/NRSF to Control Neural Stem Cell Proliferation and Differentiation |
| title_full_unstemmed | Microcephaly Gene Links Trithorax and REST/NRSF to Control Neural Stem Cell Proliferation and Differentiation |
| title_short | Microcephaly Gene Links Trithorax and REST/NRSF to Control Neural Stem Cell Proliferation and Differentiation |
| title_sort | microcephaly gene links trithorax and rest nrsf to control neural stem cell proliferation and differentiation |
| url | http://hdl.handle.net/1721.1/91519 |
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