Tcf/Lef repressors differentially regulate Shh-Gli target gene activation thresholds to generate progenitor patterning in the developing CNS

During neural tube development, Shh signaling through Gli transcription factors is necessary to establish five distinct ventral progenitor domains that give rise to unique classes of neurons and glia that arise in specific positions along the dorsoventral axis. These cells are generated from progeni...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Development (Cambridge) 2011-09, Vol.138 (17), p.3711-3721
Hauptverfasser: Wang, Hui, Lei, Qiubo, Oosterveen, Tony, Ericson, Johan, Matise, Michael P
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page 3721
container_issue 17
container_start_page 3711
container_title Development (Cambridge)
container_volume 138
creator Wang, Hui
Lei, Qiubo
Oosterveen, Tony
Ericson, Johan
Matise, Michael P
description During neural tube development, Shh signaling through Gli transcription factors is necessary to establish five distinct ventral progenitor domains that give rise to unique classes of neurons and glia that arise in specific positions along the dorsoventral axis. These cells are generated from progenitors that display distinct transcription factor gene expression profiles in specific domains in the ventricular zone. However, the molecular genetic mechanisms that control the differential spatiotemporal transcriptional responses of progenitor target genes to graded Shh-Gli signaling remain unclear. The current study demonstrates a role for Tcf/Lef repressor activity in this process. We show that Tcf3 and Tcf7L2 (Tcf4) are required for proper ventral patterning and function by independently regulating two Shh-Gli target genes, Nkx2.2 and Olig2, which are initially induced in a common pool of progenitors that ultimately segregate into unique territories giving rise to distinct progeny. Genetic and functional studies in vivo show that Tcf transcriptional repressors selectively elevate the strength and duration of Gli activity necessary to induce Nkx2.2, but have no effect on Olig2, and thereby contribute to the establishment of their distinct expression domains in cooperation with graded Shh signaling. Together, our data reveal a Shh-Gli-independent transcriptional input that is required to shape the precise spatial and temporal response to extracellular morphogen signaling information during lineage segregation in the CNS.
doi_str_mv 10.1242/dev.068270
format Article
fullrecord <record><control><sourceid>proquest_swepu</sourceid><recordid>TN_cdi_swepub_primary_oai_swepub_ki_se_542971</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>902365306</sourcerecordid><originalsourceid>FETCH-LOGICAL-c563t-f115b26ea8c3e6d1400fe93c1ab8c327711a42e85b43f022600b48a60fcf8c7c3</originalsourceid><addsrcrecordid>eNqFks9u1DAQxiMEotvChQdAviEhpfWfxI4vSGgFBWkFh5az5TjjrMEbB9u7Vd-Bh66X3RZ6QJw8mvl9n2bGU1WvCD4ntKEXA-zOMe-owE-qBWmEqCWh8mm1wLLFNZGSnFSnKX3HGDMuxPPqhBIh2oZ0i-rXtbEXK7AowhwhpRATGpy1EGHKTnt_Wyrj1usM6Gq9ri-9Q1nHETIaYQKkTXY7nV2YUF4Xg3XwQ0I5_K7GvWqOocQuh4hmnTPEyU0jcnseUGkdfJj3meWXqxfVM6t9gpfH96z69vHD9fJTvfp6-Xn5flWblrNcW0LannLQnWHAB9JgbEEyQ3RfMlQIQnRDoWv7hllMKce4bzrNsTW2M8Kws6o--KYbmLe9mqPb6HirgnbqmPpRIlBtQ6UghZf_5Mt4wx_RvZBQhllphBbtu4O2ABsYTFlr1P6xxaPK5NZqDDvFSEsl5cXgzdEghp9bSFltXDLgvZ4gbJOSmDLeMvx_susYxpwQWci3B9LEkFIE-9APwWp_U6p8jDrcVIFf_z3BA3p_ROwOWULM0Q</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>883006119</pqid></control><display><type>article</type><title>Tcf/Lef repressors differentially regulate Shh-Gli target gene activation thresholds to generate progenitor patterning in the developing CNS</title><source>MEDLINE</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>SWEPUB Freely available online</source><source>Alma/SFX Local Collection</source><source>Company of Biologists</source><creator>Wang, Hui ; Lei, Qiubo ; Oosterveen, Tony ; Ericson, Johan ; Matise, Michael P</creator><creatorcontrib>Wang, Hui ; Lei, Qiubo ; Oosterveen, Tony ; Ericson, Johan ; Matise, Michael P</creatorcontrib><description>During neural tube development, Shh signaling through Gli transcription factors is necessary to establish five distinct ventral progenitor domains that give rise to unique classes of neurons and glia that arise in specific positions along the dorsoventral axis. These cells are generated from progenitors that display distinct transcription factor gene expression profiles in specific domains in the ventricular zone. However, the molecular genetic mechanisms that control the differential spatiotemporal transcriptional responses of progenitor target genes to graded Shh-Gli signaling remain unclear. The current study demonstrates a role for Tcf/Lef repressor activity in this process. We show that Tcf3 and Tcf7L2 (Tcf4) are required for proper ventral patterning and function by independently regulating two Shh-Gli target genes, Nkx2.2 and Olig2, which are initially induced in a common pool of progenitors that ultimately segregate into unique territories giving rise to distinct progeny. Genetic and functional studies in vivo show that Tcf transcriptional repressors selectively elevate the strength and duration of Gli activity necessary to induce Nkx2.2, but have no effect on Olig2, and thereby contribute to the establishment of their distinct expression domains in cooperation with graded Shh signaling. Together, our data reveal a Shh-Gli-independent transcriptional input that is required to shape the precise spatial and temporal response to extracellular morphogen signaling information during lineage segregation in the CNS.</description><identifier>ISSN: 0950-1991</identifier><identifier>ISSN: 1477-9129</identifier><identifier>EISSN: 1477-9129</identifier><identifier>DOI: 10.1242/dev.068270</identifier><identifier>PMID: 21775418</identifier><language>eng</language><publisher>England: Company of Biologists</publisher><subject>Animals ; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors - genetics ; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors - metabolism ; Basic Helix-Loop-Helix Transcription Factors - genetics ; Basic Helix-Loop-Helix Transcription Factors - metabolism ; Body Patterning - genetics ; Body Patterning - physiology ; Central Nervous System - cytology ; Central Nervous System - embryology ; Central Nervous System - metabolism ; Chick Embryo ; Chromatin Immunoprecipitation ; Electroporation ; Enhancer Elements, Genetic - genetics ; Enhancer Elements, Genetic - physiology ; Homeodomain Proteins - genetics ; Homeodomain Proteins - metabolism ; In Situ Hybridization ; Medicin och hälsovetenskap ; Mice ; Mice, Transgenic ; Nerve Tissue Proteins - genetics ; Nerve Tissue Proteins - metabolism ; Oligodendrocyte Transcription Factor 2 ; Polymerase Chain Reaction ; Spinal Cord - cytology ; Spinal Cord - embryology ; Spinal Cord - metabolism ; Stem Cells - cytology ; Stem Cells - metabolism ; Transcription Factor 4 ; Transcription Factors - genetics ; Transcription Factors - metabolism</subject><ispartof>Development (Cambridge), 2011-09, Vol.138 (17), p.3711-3721</ispartof><rights>2011.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c563t-f115b26ea8c3e6d1400fe93c1ab8c327711a42e85b43f022600b48a60fcf8c7c3</citedby><cites>FETCH-LOGICAL-c563t-f115b26ea8c3e6d1400fe93c1ab8c327711a42e85b43f022600b48a60fcf8c7c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,552,780,784,885,3678,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21775418$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttp://kipublications.ki.se/Default.aspx?queryparsed=id:123037712$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><creatorcontrib>Wang, Hui</creatorcontrib><creatorcontrib>Lei, Qiubo</creatorcontrib><creatorcontrib>Oosterveen, Tony</creatorcontrib><creatorcontrib>Ericson, Johan</creatorcontrib><creatorcontrib>Matise, Michael P</creatorcontrib><title>Tcf/Lef repressors differentially regulate Shh-Gli target gene activation thresholds to generate progenitor patterning in the developing CNS</title><title>Development (Cambridge)</title><addtitle>Development</addtitle><description>During neural tube development, Shh signaling through Gli transcription factors is necessary to establish five distinct ventral progenitor domains that give rise to unique classes of neurons and glia that arise in specific positions along the dorsoventral axis. These cells are generated from progenitors that display distinct transcription factor gene expression profiles in specific domains in the ventricular zone. However, the molecular genetic mechanisms that control the differential spatiotemporal transcriptional responses of progenitor target genes to graded Shh-Gli signaling remain unclear. The current study demonstrates a role for Tcf/Lef repressor activity in this process. We show that Tcf3 and Tcf7L2 (Tcf4) are required for proper ventral patterning and function by independently regulating two Shh-Gli target genes, Nkx2.2 and Olig2, which are initially induced in a common pool of progenitors that ultimately segregate into unique territories giving rise to distinct progeny. Genetic and functional studies in vivo show that Tcf transcriptional repressors selectively elevate the strength and duration of Gli activity necessary to induce Nkx2.2, but have no effect on Olig2, and thereby contribute to the establishment of their distinct expression domains in cooperation with graded Shh signaling. Together, our data reveal a Shh-Gli-independent transcriptional input that is required to shape the precise spatial and temporal response to extracellular morphogen signaling information during lineage segregation in the CNS.</description><subject>Animals</subject><subject>Basic Helix-Loop-Helix Leucine Zipper Transcription Factors - genetics</subject><subject>Basic Helix-Loop-Helix Leucine Zipper Transcription Factors - metabolism</subject><subject>Basic Helix-Loop-Helix Transcription Factors - genetics</subject><subject>Basic Helix-Loop-Helix Transcription Factors - metabolism</subject><subject>Body Patterning - genetics</subject><subject>Body Patterning - physiology</subject><subject>Central Nervous System - cytology</subject><subject>Central Nervous System - embryology</subject><subject>Central Nervous System - metabolism</subject><subject>Chick Embryo</subject><subject>Chromatin Immunoprecipitation</subject><subject>Electroporation</subject><subject>Enhancer Elements, Genetic - genetics</subject><subject>Enhancer Elements, Genetic - physiology</subject><subject>Homeodomain Proteins - genetics</subject><subject>Homeodomain Proteins - metabolism</subject><subject>In Situ Hybridization</subject><subject>Medicin och hälsovetenskap</subject><subject>Mice</subject><subject>Mice, Transgenic</subject><subject>Nerve Tissue Proteins - genetics</subject><subject>Nerve Tissue Proteins - metabolism</subject><subject>Oligodendrocyte Transcription Factor 2</subject><subject>Polymerase Chain Reaction</subject><subject>Spinal Cord - cytology</subject><subject>Spinal Cord - embryology</subject><subject>Spinal Cord - metabolism</subject><subject>Stem Cells - cytology</subject><subject>Stem Cells - metabolism</subject><subject>Transcription Factor 4</subject><subject>Transcription Factors - genetics</subject><subject>Transcription Factors - metabolism</subject><issn>0950-1991</issn><issn>1477-9129</issn><issn>1477-9129</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>D8T</sourceid><recordid>eNqFks9u1DAQxiMEotvChQdAviEhpfWfxI4vSGgFBWkFh5az5TjjrMEbB9u7Vd-Bh66X3RZ6QJw8mvl9n2bGU1WvCD4ntKEXA-zOMe-owE-qBWmEqCWh8mm1wLLFNZGSnFSnKX3HGDMuxPPqhBIh2oZ0i-rXtbEXK7AowhwhpRATGpy1EGHKTnt_Wyrj1usM6Gq9ri-9Q1nHETIaYQKkTXY7nV2YUF4Xg3XwQ0I5_K7GvWqOocQuh4hmnTPEyU0jcnseUGkdfJj3meWXqxfVM6t9gpfH96z69vHD9fJTvfp6-Xn5flWblrNcW0LannLQnWHAB9JgbEEyQ3RfMlQIQnRDoWv7hllMKce4bzrNsTW2M8Kws6o--KYbmLe9mqPb6HirgnbqmPpRIlBtQ6UghZf_5Mt4wx_RvZBQhllphBbtu4O2ABsYTFlr1P6xxaPK5NZqDDvFSEsl5cXgzdEghp9bSFltXDLgvZ4gbJOSmDLeMvx_susYxpwQWci3B9LEkFIE-9APwWp_U6p8jDrcVIFf_z3BA3p_ROwOWULM0Q</recordid><startdate>20110901</startdate><enddate>20110901</enddate><creator>Wang, Hui</creator><creator>Lei, Qiubo</creator><creator>Oosterveen, Tony</creator><creator>Ericson, Johan</creator><creator>Matise, Michael P</creator><general>Company of Biologists</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>7X8</scope><scope>7TK</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>5PM</scope><scope>ADTPV</scope><scope>AOWAS</scope><scope>D8T</scope><scope>ZZAVC</scope></search><sort><creationdate>20110901</creationdate><title>Tcf/Lef repressors differentially regulate Shh-Gli target gene activation thresholds to generate progenitor patterning in the developing CNS</title><author>Wang, Hui ; Lei, Qiubo ; Oosterveen, Tony ; Ericson, Johan ; Matise, Michael P</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c563t-f115b26ea8c3e6d1400fe93c1ab8c327711a42e85b43f022600b48a60fcf8c7c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Animals</topic><topic>Basic Helix-Loop-Helix Leucine Zipper Transcription Factors - genetics</topic><topic>Basic Helix-Loop-Helix Leucine Zipper Transcription Factors - metabolism</topic><topic>Basic Helix-Loop-Helix Transcription Factors - genetics</topic><topic>Basic Helix-Loop-Helix Transcription Factors - metabolism</topic><topic>Body Patterning - genetics</topic><topic>Body Patterning - physiology</topic><topic>Central Nervous System - cytology</topic><topic>Central Nervous System - embryology</topic><topic>Central Nervous System - metabolism</topic><topic>Chick Embryo</topic><topic>Chromatin Immunoprecipitation</topic><topic>Electroporation</topic><topic>Enhancer Elements, Genetic - genetics</topic><topic>Enhancer Elements, Genetic - physiology</topic><topic>Homeodomain Proteins - genetics</topic><topic>Homeodomain Proteins - metabolism</topic><topic>In Situ Hybridization</topic><topic>Medicin och hälsovetenskap</topic><topic>Mice</topic><topic>Mice, Transgenic</topic><topic>Nerve Tissue Proteins - genetics</topic><topic>Nerve Tissue Proteins - metabolism</topic><topic>Oligodendrocyte Transcription Factor 2</topic><topic>Polymerase Chain Reaction</topic><topic>Spinal Cord - cytology</topic><topic>Spinal Cord - embryology</topic><topic>Spinal Cord - metabolism</topic><topic>Stem Cells - cytology</topic><topic>Stem Cells - metabolism</topic><topic>Transcription Factor 4</topic><topic>Transcription Factors - genetics</topic><topic>Transcription Factors - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wang, Hui</creatorcontrib><creatorcontrib>Lei, Qiubo</creatorcontrib><creatorcontrib>Oosterveen, Tony</creatorcontrib><creatorcontrib>Ericson, Johan</creatorcontrib><creatorcontrib>Matise, Michael P</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Neurosciences Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><collection>SwePub</collection><collection>SwePub Articles</collection><collection>SWEPUB Freely available online</collection><collection>SwePub Articles full text</collection><jtitle>Development (Cambridge)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, Hui</au><au>Lei, Qiubo</au><au>Oosterveen, Tony</au><au>Ericson, Johan</au><au>Matise, Michael P</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Tcf/Lef repressors differentially regulate Shh-Gli target gene activation thresholds to generate progenitor patterning in the developing CNS</atitle><jtitle>Development (Cambridge)</jtitle><addtitle>Development</addtitle><date>2011-09-01</date><risdate>2011</risdate><volume>138</volume><issue>17</issue><spage>3711</spage><epage>3721</epage><pages>3711-3721</pages><issn>0950-1991</issn><issn>1477-9129</issn><eissn>1477-9129</eissn><abstract>During neural tube development, Shh signaling through Gli transcription factors is necessary to establish five distinct ventral progenitor domains that give rise to unique classes of neurons and glia that arise in specific positions along the dorsoventral axis. These cells are generated from progenitors that display distinct transcription factor gene expression profiles in specific domains in the ventricular zone. However, the molecular genetic mechanisms that control the differential spatiotemporal transcriptional responses of progenitor target genes to graded Shh-Gli signaling remain unclear. The current study demonstrates a role for Tcf/Lef repressor activity in this process. We show that Tcf3 and Tcf7L2 (Tcf4) are required for proper ventral patterning and function by independently regulating two Shh-Gli target genes, Nkx2.2 and Olig2, which are initially induced in a common pool of progenitors that ultimately segregate into unique territories giving rise to distinct progeny. Genetic and functional studies in vivo show that Tcf transcriptional repressors selectively elevate the strength and duration of Gli activity necessary to induce Nkx2.2, but have no effect on Olig2, and thereby contribute to the establishment of their distinct expression domains in cooperation with graded Shh signaling. Together, our data reveal a Shh-Gli-independent transcriptional input that is required to shape the precise spatial and temporal response to extracellular morphogen signaling information during lineage segregation in the CNS.</abstract><cop>England</cop><pub>Company of Biologists</pub><pmid>21775418</pmid><doi>10.1242/dev.068270</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 0950-1991
ispartof Development (Cambridge), 2011-09, Vol.138 (17), p.3711-3721
issn 0950-1991
1477-9129
1477-9129
language eng
recordid cdi_swepub_primary_oai_swepub_ki_se_542971
source MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; SWEPUB Freely available online; Alma/SFX Local Collection; Company of Biologists
subjects Animals
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors - genetics
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors - metabolism
Basic Helix-Loop-Helix Transcription Factors - genetics
Basic Helix-Loop-Helix Transcription Factors - metabolism
Body Patterning - genetics
Body Patterning - physiology
Central Nervous System - cytology
Central Nervous System - embryology
Central Nervous System - metabolism
Chick Embryo
Chromatin Immunoprecipitation
Electroporation
Enhancer Elements, Genetic - genetics
Enhancer Elements, Genetic - physiology
Homeodomain Proteins - genetics
Homeodomain Proteins - metabolism
In Situ Hybridization
Medicin och hälsovetenskap
Mice
Mice, Transgenic
Nerve Tissue Proteins - genetics
Nerve Tissue Proteins - metabolism
Oligodendrocyte Transcription Factor 2
Polymerase Chain Reaction
Spinal Cord - cytology
Spinal Cord - embryology
Spinal Cord - metabolism
Stem Cells - cytology
Stem Cells - metabolism
Transcription Factor 4
Transcription Factors - genetics
Transcription Factors - metabolism
title Tcf/Lef repressors differentially regulate Shh-Gli target gene activation thresholds to generate progenitor patterning in the developing CNS
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-06T00%3A09%3A30IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_swepu&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Tcf/Lef%20repressors%20differentially%20regulate%20Shh-Gli%20target%20gene%20activation%20thresholds%20to%20generate%20progenitor%20patterning%20in%20the%20developing%20CNS&rft.jtitle=Development%20(Cambridge)&rft.au=Wang,%20Hui&rft.date=2011-09-01&rft.volume=138&rft.issue=17&rft.spage=3711&rft.epage=3721&rft.pages=3711-3721&rft.issn=0950-1991&rft.eissn=1477-9129&rft_id=info:doi/10.1242/dev.068270&rft_dat=%3Cproquest_swepu%3E902365306%3C/proquest_swepu%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=883006119&rft_id=info:pmid/21775418&rfr_iscdi=true