Hypopituitarism in Sox3 null mutants correlates with altered NG2-glia in the median eminence and is influenced by aspirin and gut microbiota
The median eminence (ME), located at the base of the hypothalamus, is an essential centre of information exchange between the brain and the pituitary. We and others previously showed that mutations and duplications affecting the transcription factor SOX3/Sox3 result in hypopituitarism, and this is l...
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description | The median eminence (ME), located at the base of the hypothalamus, is an essential centre of information exchange between the brain and the pituitary. We and others previously showed that mutations and duplications affecting the transcription factor SOX3/Sox3 result in hypopituitarism, and this is likely of hypothalamic origin. We demonstrate here that the absence of Sox3 predominantly affects the ME with phenotypes that first occur in juvenile animals, despite the embryonic onset of SOX3 expression. In the pituitary, reduction in hormone levels correlates with a lack of endocrine cell maturation. In parallel, ME NG2-glia renewal and oligodendrocytic differentiation potential are affected. We further show that low-dose aspirin treatment, which is known to affect NG2-glia, or changes in gut microbiota, rescue both proliferative defects and hypopituitarism in Sox3 mutants. Our study highlights a central role of NG2-glia for ME function during a transitional period of post-natal development and indicates their sensitivity to extrinsic signals. |
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We and others previously showed that mutations and duplications affecting the transcription factor SOX3/Sox3 result in hypopituitarism, and this is likely of hypothalamic origin. We demonstrate here that the absence of Sox3 predominantly affects the ME with phenotypes that first occur in juvenile animals, despite the embryonic onset of SOX3 expression. In the pituitary, reduction in hormone levels correlates with a lack of endocrine cell maturation. In parallel, ME NG2-glia renewal and oligodendrocytic differentiation potential are affected. We further show that low-dose aspirin treatment, which is known to affect NG2-glia, or changes in gut microbiota, rescue both proliferative defects and hypopituitarism in Sox3 mutants. Our study highlights a central role of NG2-glia for ME function during a transitional period of post-natal development and indicates their sensitivity to extrinsic signals.</description><identifier>ISSN: 1553-7404</identifier><identifier>ISSN: 1553-7390</identifier><identifier>EISSN: 1553-7404</identifier><identifier>DOI: 10.1371/journal.pgen.1011395</identifier><identifier>PMID: 39325695</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Analysis ; Animals ; Aspirin ; Aspirin - pharmacology ; Biology and Life Sciences ; Cell Differentiation ; Dosage and administration ; Gastrointestinal Microbiome - genetics ; Hypopituitarism ; Hypopituitarism - genetics ; Identification and classification ; Male ; Median Eminence - metabolism ; Medicine and Health Sciences ; Mice ; Mice, Knockout ; Microbiota (Symbiotic organisms) ; Neuroglia ; Neuroglia - metabolism ; Pituitary Gland - metabolism ; Research and Analysis Methods ; SOXB1 Transcription Factors - genetics ; SOXB1 Transcription Factors - metabolism ; Transcription factors</subject><ispartof>PLoS genetics, 2024-09, Vol.20 (9), p.e1011395</ispartof><rights>Copyright: © 2024 Galichet et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</rights><rights>COPYRIGHT 2024 Public Library of Science</rights><rights>2024 Galichet et al 2024 Galichet et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c488t-181a66f347c7179153f0f017dcbd0776360c9c066b737dc68864bade28ded44f3</cites><orcidid>0000-0003-0711-5452 ; 0000-0001-9364-4179 ; 0000-0003-0244-9381</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11426531/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11426531/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2927,27923,27924,53790,53792</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39325695$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Hamilton, Bruce A.</contributor><creatorcontrib>Galichet, Christophe</creatorcontrib><creatorcontrib>Rizzoti, Karine</creatorcontrib><creatorcontrib>Lovell-Badge, Robin</creatorcontrib><title>Hypopituitarism in Sox3 null mutants correlates with altered NG2-glia in the median eminence and is influenced by aspirin and gut microbiota</title><title>PLoS genetics</title><addtitle>PLoS Genet</addtitle><description>The median eminence (ME), located at the base of the hypothalamus, is an essential centre of information exchange between the brain and the pituitary. We and others previously showed that mutations and duplications affecting the transcription factor SOX3/Sox3 result in hypopituitarism, and this is likely of hypothalamic origin. We demonstrate here that the absence of Sox3 predominantly affects the ME with phenotypes that first occur in juvenile animals, despite the embryonic onset of SOX3 expression. In the pituitary, reduction in hormone levels correlates with a lack of endocrine cell maturation. In parallel, ME NG2-glia renewal and oligodendrocytic differentiation potential are affected. We further show that low-dose aspirin treatment, which is known to affect NG2-glia, or changes in gut microbiota, rescue both proliferative defects and hypopituitarism in Sox3 mutants. Our study highlights a central role of NG2-glia for ME function during a transitional period of post-natal development and indicates their sensitivity to extrinsic signals.</description><subject>Analysis</subject><subject>Animals</subject><subject>Aspirin</subject><subject>Aspirin - pharmacology</subject><subject>Biology and Life Sciences</subject><subject>Cell Differentiation</subject><subject>Dosage and administration</subject><subject>Gastrointestinal Microbiome - genetics</subject><subject>Hypopituitarism</subject><subject>Hypopituitarism - genetics</subject><subject>Identification and classification</subject><subject>Male</subject><subject>Median Eminence - metabolism</subject><subject>Medicine and Health Sciences</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>Microbiota (Symbiotic organisms)</subject><subject>Neuroglia</subject><subject>Neuroglia - metabolism</subject><subject>Pituitary Gland - metabolism</subject><subject>Research and Analysis Methods</subject><subject>SOXB1 Transcription Factors - genetics</subject><subject>SOXB1 Transcription Factors - metabolism</subject><subject>Transcription factors</subject><issn>1553-7404</issn><issn>1553-7390</issn><issn>1553-7404</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqVkt9qFDEUxgdRbK2-gUhAEL3YNZnMZGaupBRtC6UFq96GTObMTEomGfNHu-_gQ5th17ILXii5SDjn932Ec74se0nwmtCKvL-z0Rmh1_MAZk0wIbQpH2XHpCzpqipw8XjvfZQ98_4OY1rWTfU0O6INzUvWlMfZr4vNbGcVogrCKT8hZdCtvafIRK3RFIMwwSNpnQMtAnj0U4URCR3AQYeuz_PVoJVYVGEENEGnhEEwKQNGAhKmQ8qnbq_jUuhQu0HCz8olwdIcYkCTks62ygbxPHvSC-3hxe4-yb5--vjl7GJ1dXN-eXZ6tZJFXYcVqYlgrKdFJStSNaSkPe4xqTrZdriqGGVYNhIz1lY0FVlds6IVHeR1B11R9PQk-7D1nWObvizBBCc0n52ahNtwKxQ_7Bg18sH-4IQUOSspSQ5vdw7Ofo_gA5-Ul6C1MGCj55QQTJumKXBCX2_RQWjgaRQ2WcoF56d1MiwJy8tErf9CpdOlYUproFepfiB4dyBITID7MIjoPb-8_fwf7PW_szffDtk3e-wIKRajtzoGZY0_BIstmDbtvYP-YdYE8yXNfJdmvqSZ79KcZK_29_Qg-hNf-hsIGfH4</recordid><startdate>20240926</startdate><enddate>20240926</enddate><creator>Galichet, Christophe</creator><creator>Rizzoti, Karine</creator><creator>Lovell-Badge, Robin</creator><general>Public Library of Science</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISN</scope><scope>ISR</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-0711-5452</orcidid><orcidid>https://orcid.org/0000-0001-9364-4179</orcidid><orcidid>https://orcid.org/0000-0003-0244-9381</orcidid></search><sort><creationdate>20240926</creationdate><title>Hypopituitarism in Sox3 null mutants correlates with altered NG2-glia in the median eminence and is influenced by aspirin and gut microbiota</title><author>Galichet, Christophe ; Rizzoti, Karine ; Lovell-Badge, Robin</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c488t-181a66f347c7179153f0f017dcbd0776360c9c066b737dc68864bade28ded44f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Analysis</topic><topic>Animals</topic><topic>Aspirin</topic><topic>Aspirin - pharmacology</topic><topic>Biology and Life Sciences</topic><topic>Cell Differentiation</topic><topic>Dosage and administration</topic><topic>Gastrointestinal Microbiome - genetics</topic><topic>Hypopituitarism</topic><topic>Hypopituitarism - genetics</topic><topic>Identification and classification</topic><topic>Male</topic><topic>Median Eminence - metabolism</topic><topic>Medicine and Health Sciences</topic><topic>Mice</topic><topic>Mice, Knockout</topic><topic>Microbiota (Symbiotic organisms)</topic><topic>Neuroglia</topic><topic>Neuroglia - metabolism</topic><topic>Pituitary Gland - metabolism</topic><topic>Research and Analysis Methods</topic><topic>SOXB1 Transcription Factors - genetics</topic><topic>SOXB1 Transcription Factors - metabolism</topic><topic>Transcription factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Galichet, Christophe</creatorcontrib><creatorcontrib>Rizzoti, Karine</creatorcontrib><creatorcontrib>Lovell-Badge, Robin</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Canada</collection><collection>Gale In Context: Science</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>PLoS genetics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Galichet, Christophe</au><au>Rizzoti, Karine</au><au>Lovell-Badge, Robin</au><au>Hamilton, Bruce A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Hypopituitarism in Sox3 null mutants correlates with altered NG2-glia in the median eminence and is influenced by aspirin and gut microbiota</atitle><jtitle>PLoS genetics</jtitle><addtitle>PLoS Genet</addtitle><date>2024-09-26</date><risdate>2024</risdate><volume>20</volume><issue>9</issue><spage>e1011395</spage><pages>e1011395-</pages><issn>1553-7404</issn><issn>1553-7390</issn><eissn>1553-7404</eissn><abstract>The median eminence (ME), located at the base of the hypothalamus, is an essential centre of information exchange between the brain and the pituitary. We and others previously showed that mutations and duplications affecting the transcription factor SOX3/Sox3 result in hypopituitarism, and this is likely of hypothalamic origin. We demonstrate here that the absence of Sox3 predominantly affects the ME with phenotypes that first occur in juvenile animals, despite the embryonic onset of SOX3 expression. In the pituitary, reduction in hormone levels correlates with a lack of endocrine cell maturation. In parallel, ME NG2-glia renewal and oligodendrocytic differentiation potential are affected. We further show that low-dose aspirin treatment, which is known to affect NG2-glia, or changes in gut microbiota, rescue both proliferative defects and hypopituitarism in Sox3 mutants. 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subjects | Analysis Animals Aspirin Aspirin - pharmacology Biology and Life Sciences Cell Differentiation Dosage and administration Gastrointestinal Microbiome - genetics Hypopituitarism Hypopituitarism - genetics Identification and classification Male Median Eminence - metabolism Medicine and Health Sciences Mice Mice, Knockout Microbiota (Symbiotic organisms) Neuroglia Neuroglia - metabolism Pituitary Gland - metabolism Research and Analysis Methods SOXB1 Transcription Factors - genetics SOXB1 Transcription Factors - metabolism Transcription factors |
title | Hypopituitarism in Sox3 null mutants correlates with altered NG2-glia in the median eminence and is influenced by aspirin and gut microbiota |
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