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Hes6 Inhibits Astrocyte Differentiation and Promotes Neurogenesis through Different Mechanisms
The mechanisms regulating the generation of cell diversity in the mammalian cerebral cortex are beginning to be elucidated. In that regard, Hairy/Enhancer of split (Hes) 1 and 5 are basic helix-loop-helix (bHLH) factors that inhibit the differentiation of pluripotent cortical progenitors into neuron...
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| Published in: | The Journal of neuroscience 2006-10, Vol.26 (43), p.11061-11071 |
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| container_end_page | 11071 |
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| container_title | The Journal of neuroscience |
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| creator | Jhas, Sumit Ciura, Sorana Belanger-Jasmin, Stephanie Dong, Zhifeng Llamosas, Estelle Theriault, Francesca M Joachim, Kerline Tang, Yeman Liu, Lauren Liu, Jisheng Stifani, Stefano |
| description | The mechanisms regulating the generation of cell diversity in the mammalian cerebral cortex are beginning to be elucidated. In that regard, Hairy/Enhancer of split (Hes) 1 and 5 are basic helix-loop-helix (bHLH) factors that inhibit the differentiation of pluripotent cortical progenitors into neurons. In contrast, a related Hes family member termed Hes6 promotes neurogenesis. It is shown here that knockdown of endogenous Hes6 causes supernumerary cortical progenitors to differentiate into cells that exhibit an astrocytic morphology and express the astrocyte marker protein GFAP. Conversely, exogenous Hes6 expression in cortical progenitors inhibits astrocyte differentiation. The negative effect of Hes6 on astrocyte differentiation is independent of its ability to promote neuronal differentiation. We also show that neither its proneuronal nor its anti-gliogenic functions appear to depend on Hes6 ability to bind to DNA via the basic arm of its bHLH domain. Both of these activities require Hes6 to be localized to nuclei, but only its anti-gliogenic function depends on two short peptides, LNHLL and WRPW, that are conserved in all Hes6 proteins. These findings suggest that Hes6 is an important regulator of the neurogenic phase of cortical development by promoting the neuronal fate while suppressing astrocyte differentiation. They suggest further that separate molecular mechanisms underlie the proneuronal and anti-gliogenic activities of Hes6 in cortical progenitor cells. |
| doi_str_mv | 10.1523/JNEUROSCI.1358-06.2006 |
| format | article |
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In that regard, Hairy/Enhancer of split (Hes) 1 and 5 are basic helix-loop-helix (bHLH) factors that inhibit the differentiation of pluripotent cortical progenitors into neurons. In contrast, a related Hes family member termed Hes6 promotes neurogenesis. It is shown here that knockdown of endogenous Hes6 causes supernumerary cortical progenitors to differentiate into cells that exhibit an astrocytic morphology and express the astrocyte marker protein GFAP. Conversely, exogenous Hes6 expression in cortical progenitors inhibits astrocyte differentiation. The negative effect of Hes6 on astrocyte differentiation is independent of its ability to promote neuronal differentiation. We also show that neither its proneuronal nor its anti-gliogenic functions appear to depend on Hes6 ability to bind to DNA via the basic arm of its bHLH domain. Both of these activities require Hes6 to be localized to nuclei, but only its anti-gliogenic function depends on two short peptides, LNHLL and WRPW, that are conserved in all Hes6 proteins. These findings suggest that Hes6 is an important regulator of the neurogenic phase of cortical development by promoting the neuronal fate while suppressing astrocyte differentiation. They suggest further that separate molecular mechanisms underlie the proneuronal and anti-gliogenic activities of Hes6 in cortical progenitor cells.</description><identifier>ISSN: 0270-6474</identifier><identifier>EISSN: 1529-2401</identifier><identifier>DOI: 10.1523/JNEUROSCI.1358-06.2006</identifier><identifier>PMID: 17065448</identifier><language>eng</language><publisher>United States: Soc Neuroscience</publisher><subject>Animals ; Astrocytes - cytology ; Astrocytes - metabolism ; Basic Helix-Loop-Helix Transcription Factors - biosynthesis ; Basic Helix-Loop-Helix Transcription Factors - genetics ; Basic Helix-Loop-Helix Transcription Factors - physiology ; Cell Differentiation - physiology ; Cell Line ; Cells, Cultured ; Growth Inhibitors - physiology ; Humans ; Mice ; Neural Inhibition - physiology ; Repressor Proteins - biosynthesis ; Repressor Proteins - genetics ; Repressor Proteins - physiology</subject><ispartof>The Journal of neuroscience, 2006-10, Vol.26 (43), p.11061-11071</ispartof><rights>Copyright © 2006 Society for Neuroscience 0270-6474/06/2611061-11$15.00/0 2006</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c476t-231ab3b0f88c9866846ea3cf9069f4c5a9457fc9a3695a43b1be7d7f35b279c53</citedby><cites>FETCH-LOGICAL-c476t-231ab3b0f88c9866846ea3cf9069f4c5a9457fc9a3695a43b1be7d7f35b279c53</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6674651/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6674651/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,315,733,786,790,891,27957,27958,53827,53829</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17065448$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Jhas, Sumit</creatorcontrib><creatorcontrib>Ciura, Sorana</creatorcontrib><creatorcontrib>Belanger-Jasmin, Stephanie</creatorcontrib><creatorcontrib>Dong, Zhifeng</creatorcontrib><creatorcontrib>Llamosas, Estelle</creatorcontrib><creatorcontrib>Theriault, Francesca M</creatorcontrib><creatorcontrib>Joachim, Kerline</creatorcontrib><creatorcontrib>Tang, Yeman</creatorcontrib><creatorcontrib>Liu, Lauren</creatorcontrib><creatorcontrib>Liu, Jisheng</creatorcontrib><creatorcontrib>Stifani, Stefano</creatorcontrib><title>Hes6 Inhibits Astrocyte Differentiation and Promotes Neurogenesis through Different Mechanisms</title><title>The Journal of neuroscience</title><addtitle>J Neurosci</addtitle><description>The mechanisms regulating the generation of cell diversity in the mammalian cerebral cortex are beginning to be elucidated. In that regard, Hairy/Enhancer of split (Hes) 1 and 5 are basic helix-loop-helix (bHLH) factors that inhibit the differentiation of pluripotent cortical progenitors into neurons. In contrast, a related Hes family member termed Hes6 promotes neurogenesis. It is shown here that knockdown of endogenous Hes6 causes supernumerary cortical progenitors to differentiate into cells that exhibit an astrocytic morphology and express the astrocyte marker protein GFAP. Conversely, exogenous Hes6 expression in cortical progenitors inhibits astrocyte differentiation. The negative effect of Hes6 on astrocyte differentiation is independent of its ability to promote neuronal differentiation. We also show that neither its proneuronal nor its anti-gliogenic functions appear to depend on Hes6 ability to bind to DNA via the basic arm of its bHLH domain. Both of these activities require Hes6 to be localized to nuclei, but only its anti-gliogenic function depends on two short peptides, LNHLL and WRPW, that are conserved in all Hes6 proteins. These findings suggest that Hes6 is an important regulator of the neurogenic phase of cortical development by promoting the neuronal fate while suppressing astrocyte differentiation. They suggest further that separate molecular mechanisms underlie the proneuronal and anti-gliogenic activities of Hes6 in cortical progenitor cells.</description><subject>Animals</subject><subject>Astrocytes - cytology</subject><subject>Astrocytes - metabolism</subject><subject>Basic Helix-Loop-Helix Transcription Factors - biosynthesis</subject><subject>Basic Helix-Loop-Helix Transcription Factors - genetics</subject><subject>Basic Helix-Loop-Helix Transcription Factors - physiology</subject><subject>Cell Differentiation - physiology</subject><subject>Cell Line</subject><subject>Cells, Cultured</subject><subject>Growth Inhibitors - physiology</subject><subject>Humans</subject><subject>Mice</subject><subject>Neural Inhibition - physiology</subject><subject>Repressor Proteins - biosynthesis</subject><subject>Repressor Proteins - genetics</subject><subject>Repressor Proteins - physiology</subject><issn>0270-6474</issn><issn>1529-2401</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><recordid>eNqFkcFu1DAQhi0EokvhFaqcEJcsdmyP4wtStRS6qLQI6BXL8Y43Rklc7IRV356sdtXCidMc5vt_zegj5IzRJZMVf_vp-uL268231XrJuKxLCsuKUnhCFvNWl5Wg7ClZ0ErREoQSJ-RFzj8ppYoy9ZycMEVBClEvyI9LzFCshzY0YczFeR5TdPcjFu-D95hwGIMdQxwKO2yKLyn2ccRcXOOU4hYHzCEXY5vitG0fE8VndK0dQu7zS_LM2y7jq-M8JbcfLr6vLsurm4_r1flV6YSCsaw4sw1vqK9rp2uAWgBa7rymoL1w0mohlXfactDSCt6wBtVGeS6bSmkn-Sl5d-i9m5oeN26-ItnO3KXQ23Rvog3m380QWrONvw2AEiDZXPD6WJDirwnzaPqQHXadHTBO2UCtNQgQ_wWZnn1Uqp5BOIAuxZwT-odrGDV7h-bBodk7NBTM3uEcPPv7l8fYUdoMvDkAbdi2u5DQ5N523Ywzs9vtKjCCG8YoMP4HgUWpFg</recordid><startdate>20061025</startdate><enddate>20061025</enddate><creator>Jhas, Sumit</creator><creator>Ciura, Sorana</creator><creator>Belanger-Jasmin, Stephanie</creator><creator>Dong, Zhifeng</creator><creator>Llamosas, Estelle</creator><creator>Theriault, Francesca M</creator><creator>Joachim, Kerline</creator><creator>Tang, Yeman</creator><creator>Liu, Lauren</creator><creator>Liu, Jisheng</creator><creator>Stifani, Stefano</creator><general>Soc Neuroscience</general><general>Society for Neuroscience</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>7TK</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20061025</creationdate><title>Hes6 Inhibits Astrocyte Differentiation and Promotes Neurogenesis through Different Mechanisms</title><author>Jhas, Sumit ; Ciura, Sorana ; Belanger-Jasmin, Stephanie ; Dong, Zhifeng ; Llamosas, Estelle ; Theriault, Francesca M ; Joachim, Kerline ; Tang, Yeman ; Liu, Lauren ; Liu, Jisheng ; Stifani, Stefano</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c476t-231ab3b0f88c9866846ea3cf9069f4c5a9457fc9a3695a43b1be7d7f35b279c53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Animals</topic><topic>Astrocytes - cytology</topic><topic>Astrocytes - metabolism</topic><topic>Basic Helix-Loop-Helix Transcription Factors - biosynthesis</topic><topic>Basic Helix-Loop-Helix Transcription Factors - genetics</topic><topic>Basic Helix-Loop-Helix Transcription Factors - physiology</topic><topic>Cell Differentiation - physiology</topic><topic>Cell Line</topic><topic>Cells, Cultured</topic><topic>Growth Inhibitors - physiology</topic><topic>Humans</topic><topic>Mice</topic><topic>Neural Inhibition - physiology</topic><topic>Repressor Proteins - biosynthesis</topic><topic>Repressor Proteins - genetics</topic><topic>Repressor Proteins - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Jhas, Sumit</creatorcontrib><creatorcontrib>Ciura, Sorana</creatorcontrib><creatorcontrib>Belanger-Jasmin, Stephanie</creatorcontrib><creatorcontrib>Dong, Zhifeng</creatorcontrib><creatorcontrib>Llamosas, Estelle</creatorcontrib><creatorcontrib>Theriault, Francesca M</creatorcontrib><creatorcontrib>Joachim, Kerline</creatorcontrib><creatorcontrib>Tang, Yeman</creatorcontrib><creatorcontrib>Liu, Lauren</creatorcontrib><creatorcontrib>Liu, Jisheng</creatorcontrib><creatorcontrib>Stifani, Stefano</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of neuroscience</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jhas, Sumit</au><au>Ciura, Sorana</au><au>Belanger-Jasmin, Stephanie</au><au>Dong, Zhifeng</au><au>Llamosas, Estelle</au><au>Theriault, Francesca M</au><au>Joachim, Kerline</au><au>Tang, Yeman</au><au>Liu, Lauren</au><au>Liu, Jisheng</au><au>Stifani, Stefano</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Hes6 Inhibits Astrocyte Differentiation and Promotes Neurogenesis through Different Mechanisms</atitle><jtitle>The Journal of neuroscience</jtitle><addtitle>J Neurosci</addtitle><date>2006-10-25</date><risdate>2006</risdate><volume>26</volume><issue>43</issue><spage>11061</spage><epage>11071</epage><pages>11061-11071</pages><issn>0270-6474</issn><eissn>1529-2401</eissn><notes>ObjectType-Article-1</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-2</notes><notes>content type line 23</notes><notes>S.C. and S.B.-J. contributed equally to this work.</notes><abstract>The mechanisms regulating the generation of cell diversity in the mammalian cerebral cortex are beginning to be elucidated. In that regard, Hairy/Enhancer of split (Hes) 1 and 5 are basic helix-loop-helix (bHLH) factors that inhibit the differentiation of pluripotent cortical progenitors into neurons. In contrast, a related Hes family member termed Hes6 promotes neurogenesis. It is shown here that knockdown of endogenous Hes6 causes supernumerary cortical progenitors to differentiate into cells that exhibit an astrocytic morphology and express the astrocyte marker protein GFAP. Conversely, exogenous Hes6 expression in cortical progenitors inhibits astrocyte differentiation. The negative effect of Hes6 on astrocyte differentiation is independent of its ability to promote neuronal differentiation. We also show that neither its proneuronal nor its anti-gliogenic functions appear to depend on Hes6 ability to bind to DNA via the basic arm of its bHLH domain. Both of these activities require Hes6 to be localized to nuclei, but only its anti-gliogenic function depends on two short peptides, LNHLL and WRPW, that are conserved in all Hes6 proteins. These findings suggest that Hes6 is an important regulator of the neurogenic phase of cortical development by promoting the neuronal fate while suppressing astrocyte differentiation. They suggest further that separate molecular mechanisms underlie the proneuronal and anti-gliogenic activities of Hes6 in cortical progenitor cells.</abstract><cop>United States</cop><pub>Soc Neuroscience</pub><pmid>17065448</pmid><doi>10.1523/JNEUROSCI.1358-06.2006</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Astrocytes - cytology Astrocytes - metabolism Basic Helix-Loop-Helix Transcription Factors - biosynthesis Basic Helix-Loop-Helix Transcription Factors - genetics Basic Helix-Loop-Helix Transcription Factors - physiology Cell Differentiation - physiology Cell Line Cells, Cultured Growth Inhibitors - physiology Humans Mice Neural Inhibition - physiology Repressor Proteins - biosynthesis Repressor Proteins - genetics Repressor Proteins - physiology |
| title | Hes6 Inhibits Astrocyte Differentiation and Promotes Neurogenesis through Different Mechanisms |
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