Loss of Gsx1 and Gsx2 function rescues distinct phenotypes in Dlx1/2 mutants
Mice lacking the Dlx1 and Dlx2 homeobox genes (Dlx1/2 mutants) have severe deficits in subpallial differentiation, including overexpression of the Gsx1 and Gsx2 homeobox genes. To investigate whether Gsx overexpression contributes to the Dlx1/2 mutant phenotypes, we made compound loss‐of‐function mu...
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| Veröffentlicht in: | Journal of comparative neurology (1911) 2013-05, Vol.521 (7), p.1561-1584 |
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| container_title | Journal of comparative neurology (1911) |
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| creator | Wang, Bei Long, Jason E. Flandin, Pierre Pla, Ramon Waclaw, Ronald R. Campbell, Kenneth Rubenstein, John L.R. |
| description | Mice lacking the Dlx1 and Dlx2 homeobox genes (Dlx1/2 mutants) have severe deficits in subpallial differentiation, including overexpression of the Gsx1 and Gsx2 homeobox genes. To investigate whether Gsx overexpression contributes to the Dlx1/2 mutant phenotypes, we made compound loss‐of‐function mutants. Eliminating Gsx2 function from the Dlx1/2 mutants rescued the increased expression of Ascl1 and Hes5 (Notch signaling mediators) and Olig2 (oligodendrogenesis mediator). In addition, Dlx1/2;Gsx2 mutants, like Dlx1/2;Ascl1 mutants, exacerbated the Gsx2 and Dlx1/2 patterning and differentiation phenotypes, particularly in the lateral ganglionic eminence (LGE) caudal ganglionic eminence (CGE), and septum, including loss of GAD1 expression. On the other hand, eliminating Gsx1 function from the Dlx1/2 mutants (Dlx1/2;Gsx1 mutants) did not severely exacerbate their phenotype; on the contrary, it resulted in a partial rescue of medial ganglionic eminence (MGE) properties, including interneuron migration to the cortex. Thus, despite their redundant properties, Gsx1 and ‐2 have distinct interactions with Dlx1 and ‐2. Gsx2 interaction is strongest in the LGE, CGE, and septum, whereas the Gsx1 interaction is strongest in the MGE. From these studies, and earlier studies, we present a model of the transcriptional network that regulates early steps of subcortical development. J. Comp. Neurol. 521:1561–1584, 2013. © 2012 Wiley Periodicals, Inc.
Dlx1/2 mutant mice have deficits in subpallial differentiation, including overexpression of Gsx1 and Gsx2. To investigate whether Gsx overexpression contributes to the Dlx1/2−/− phenotypes, we made compound loss‐of‐function mutants. Gsx2;Dlx1/2 mutants showed partial rescue of the increased expression of Notch‐signaling mediators. On the other hand, Gsx1;Dlx1/2 mutants resulted in a partial rescue of interneuron migration to the cortex. Thus, despite their redundant properties, Gsx1 and Gsx2 have distinct interactions with Dlx1 and 2. |
| doi_str_mv | 10.1002/cne.23242 |
| format | Article |
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Dlx1/2 mutant mice have deficits in subpallial differentiation, including overexpression of Gsx1 and Gsx2. To investigate whether Gsx overexpression contributes to the Dlx1/2−/− phenotypes, we made compound loss‐of‐function mutants. Gsx2;Dlx1/2 mutants showed partial rescue of the increased expression of Notch‐signaling mediators. On the other hand, Gsx1;Dlx1/2 mutants resulted in a partial rescue of interneuron migration to the cortex. Thus, despite their redundant properties, Gsx1 and Gsx2 have distinct interactions with Dlx1 and 2.</description><identifier>ISSN: 0021-9967</identifier><identifier>EISSN: 1096-9861</identifier><identifier>DOI: 10.1002/cne.23242</identifier><identifier>PMID: 23042297</identifier><language>eng</language><publisher>Hoboken: Wiley Subscription Services, Inc., A Wiley Company</publisher><subject>Animals ; ASCL1 protein ; basal ganglia ; Brain - embryology ; Brain - physiology ; CGE ; development ; Dlx ; Embryo, Mammalian ; Fluorescent Antibody Technique ; GABA ; Gsx ; Homeodomain Proteins - genetics ; Homeodomain Proteins - metabolism ; In Situ Hybridization ; interneuron ; LGE ; MGE ; Mice ; Mice, Mutant Strains ; mutant ; Neurogenesis - physiology ; Phenotype ; septum ; Transcription Factors - genetics</subject><ispartof>Journal of comparative neurology (1911), 2013-05, Vol.521 (7), p.1561-1584</ispartof><rights>Copyright © 2012 Wiley Periodicals, Inc.</rights><rights>Copyright © 2012 Wiley Periodicals, Inc. 2012</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5802-f00b285a8dc4eea2a05a4adc5744cd97fe2995fa2668e9a29536fd694f4d32b23</citedby><cites>FETCH-LOGICAL-c5802-f00b285a8dc4eea2a05a4adc5744cd97fe2995fa2668e9a29536fd694f4d32b23</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fcne.23242$$EPDF$$P50$$Gwiley$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fcne.23242$$EHTML$$P50$$Gwiley$$Hfree_for_read</linktohtml><link.rule.ids>230,314,776,780,881,1411,27903,27904,45553,45554</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23042297$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wang, Bei</creatorcontrib><creatorcontrib>Long, Jason E.</creatorcontrib><creatorcontrib>Flandin, Pierre</creatorcontrib><creatorcontrib>Pla, Ramon</creatorcontrib><creatorcontrib>Waclaw, Ronald R.</creatorcontrib><creatorcontrib>Campbell, Kenneth</creatorcontrib><creatorcontrib>Rubenstein, John L.R.</creatorcontrib><title>Loss of Gsx1 and Gsx2 function rescues distinct phenotypes in Dlx1/2 mutants</title><title>Journal of comparative neurology (1911)</title><addtitle>J. Comp. Neurol</addtitle><description>Mice lacking the Dlx1 and Dlx2 homeobox genes (Dlx1/2 mutants) have severe deficits in subpallial differentiation, including overexpression of the Gsx1 and Gsx2 homeobox genes. To investigate whether Gsx overexpression contributes to the Dlx1/2 mutant phenotypes, we made compound loss‐of‐function mutants. Eliminating Gsx2 function from the Dlx1/2 mutants rescued the increased expression of Ascl1 and Hes5 (Notch signaling mediators) and Olig2 (oligodendrogenesis mediator). In addition, Dlx1/2;Gsx2 mutants, like Dlx1/2;Ascl1 mutants, exacerbated the Gsx2 and Dlx1/2 patterning and differentiation phenotypes, particularly in the lateral ganglionic eminence (LGE) caudal ganglionic eminence (CGE), and septum, including loss of GAD1 expression. On the other hand, eliminating Gsx1 function from the Dlx1/2 mutants (Dlx1/2;Gsx1 mutants) did not severely exacerbate their phenotype; on the contrary, it resulted in a partial rescue of medial ganglionic eminence (MGE) properties, including interneuron migration to the cortex. Thus, despite their redundant properties, Gsx1 and ‐2 have distinct interactions with Dlx1 and ‐2. Gsx2 interaction is strongest in the LGE, CGE, and septum, whereas the Gsx1 interaction is strongest in the MGE. From these studies, and earlier studies, we present a model of the transcriptional network that regulates early steps of subcortical development. J. Comp. Neurol. 521:1561–1584, 2013. © 2012 Wiley Periodicals, Inc.
Dlx1/2 mutant mice have deficits in subpallial differentiation, including overexpression of Gsx1 and Gsx2. To investigate whether Gsx overexpression contributes to the Dlx1/2−/− phenotypes, we made compound loss‐of‐function mutants. Gsx2;Dlx1/2 mutants showed partial rescue of the increased expression of Notch‐signaling mediators. On the other hand, Gsx1;Dlx1/2 mutants resulted in a partial rescue of interneuron migration to the cortex. Thus, despite their redundant properties, Gsx1 and Gsx2 have distinct interactions with Dlx1 and 2.</description><subject>Animals</subject><subject>ASCL1 protein</subject><subject>basal ganglia</subject><subject>Brain - embryology</subject><subject>Brain - physiology</subject><subject>CGE</subject><subject>development</subject><subject>Dlx</subject><subject>Embryo, Mammalian</subject><subject>Fluorescent Antibody Technique</subject><subject>GABA</subject><subject>Gsx</subject><subject>Homeodomain Proteins - genetics</subject><subject>Homeodomain Proteins - metabolism</subject><subject>In Situ Hybridization</subject><subject>interneuron</subject><subject>LGE</subject><subject>MGE</subject><subject>Mice</subject><subject>Mice, Mutant Strains</subject><subject>mutant</subject><subject>Neurogenesis - physiology</subject><subject>Phenotype</subject><subject>septum</subject><subject>Transcription Factors - genetics</subject><issn>0021-9967</issn><issn>1096-9861</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>EIF</sourceid><recordid>eNqFkU1vEzEQhi0EoqFw4A8gS1zgsI2_vb4gVUkJH1EREgiJi-V4beqysYO9C8m_xyFtBEiI04xmnnntmReAxxidYYTI1EZ3Rihh5A6YYKREo1qB74JJ7eFGKSFPwINSrhFCStH2PjghFDFClJyA5TKVApOHi7LF0MRunxDox2iHkCLMrtjRFdiFMoRag5srF9Ow29RaiHDeb_GUwPU4mDiUh-CeN31xj27iKfj48uLD7FWzfLd4PTtfNpa3iDQeoRVpuWk7y5wzxCBumOksl4zZTknviFLcGyJE65QhilPhO6GYZx0lK0JPwYuD7mZcrV1nXRyy6fUmh7XJO51M0H92YrjSX9J3TQXmWPIq8OxGIKdvdb1Br0Oxru9NdGksGjPKEKb1yf-jFLdISUZlRZ_-hV6nMcd6iT0luWBC4ko9P1A219Nn54__xkjv7dTVTv3Lzso--X3RI3nrXwWmB-BH6N3u30p6dnlxK9kcJqqhbnucMPmrFpJKrj9dLvT7t-zzHM-RfkN_As2nt0o</recordid><startdate>20130501</startdate><enddate>20130501</enddate><creator>Wang, Bei</creator><creator>Long, Jason E.</creator><creator>Flandin, Pierre</creator><creator>Pla, Ramon</creator><creator>Waclaw, Ronald R.</creator><creator>Campbell, Kenneth</creator><creator>Rubenstein, John L.R.</creator><general>Wiley Subscription Services, Inc., A Wiley Company</general><general>Wiley Subscription Services, Inc</general><scope>BSCLL</scope><scope>24P</scope><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>7QR</scope><scope>7TK</scope><scope>8FD</scope><scope>FR3</scope><scope>K9.</scope><scope>P64</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20130501</creationdate><title>Loss of Gsx1 and Gsx2 function rescues distinct phenotypes in Dlx1/2 mutants</title><author>Wang, Bei ; Long, Jason E. ; Flandin, Pierre ; Pla, Ramon ; Waclaw, Ronald R. ; Campbell, Kenneth ; Rubenstein, John L.R.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5802-f00b285a8dc4eea2a05a4adc5744cd97fe2995fa2668e9a29536fd694f4d32b23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Animals</topic><topic>ASCL1 protein</topic><topic>basal ganglia</topic><topic>Brain - embryology</topic><topic>Brain - physiology</topic><topic>CGE</topic><topic>development</topic><topic>Dlx</topic><topic>Embryo, Mammalian</topic><topic>Fluorescent Antibody Technique</topic><topic>GABA</topic><topic>Gsx</topic><topic>Homeodomain Proteins - genetics</topic><topic>Homeodomain Proteins - metabolism</topic><topic>In Situ Hybridization</topic><topic>interneuron</topic><topic>LGE</topic><topic>MGE</topic><topic>Mice</topic><topic>Mice, Mutant Strains</topic><topic>mutant</topic><topic>Neurogenesis - physiology</topic><topic>Phenotype</topic><topic>septum</topic><topic>Transcription Factors - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wang, Bei</creatorcontrib><creatorcontrib>Long, Jason E.</creatorcontrib><creatorcontrib>Flandin, Pierre</creatorcontrib><creatorcontrib>Pla, Ramon</creatorcontrib><creatorcontrib>Waclaw, Ronald R.</creatorcontrib><creatorcontrib>Campbell, Kenneth</creatorcontrib><creatorcontrib>Rubenstein, John L.R.</creatorcontrib><collection>Istex</collection><collection>Wiley-Blackwell Open Access Titles</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of comparative neurology (1911)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, Bei</au><au>Long, Jason E.</au><au>Flandin, Pierre</au><au>Pla, Ramon</au><au>Waclaw, Ronald R.</au><au>Campbell, Kenneth</au><au>Rubenstein, John L.R.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Loss of Gsx1 and Gsx2 function rescues distinct phenotypes in Dlx1/2 mutants</atitle><jtitle>Journal of comparative neurology (1911)</jtitle><addtitle>J. Comp. Neurol</addtitle><date>2013-05-01</date><risdate>2013</risdate><volume>521</volume><issue>7</issue><spage>1561</spage><epage>1584</epage><pages>1561-1584</pages><issn>0021-9967</issn><eissn>1096-9861</eissn><abstract>Mice lacking the Dlx1 and Dlx2 homeobox genes (Dlx1/2 mutants) have severe deficits in subpallial differentiation, including overexpression of the Gsx1 and Gsx2 homeobox genes. To investigate whether Gsx overexpression contributes to the Dlx1/2 mutant phenotypes, we made compound loss‐of‐function mutants. Eliminating Gsx2 function from the Dlx1/2 mutants rescued the increased expression of Ascl1 and Hes5 (Notch signaling mediators) and Olig2 (oligodendrogenesis mediator). In addition, Dlx1/2;Gsx2 mutants, like Dlx1/2;Ascl1 mutants, exacerbated the Gsx2 and Dlx1/2 patterning and differentiation phenotypes, particularly in the lateral ganglionic eminence (LGE) caudal ganglionic eminence (CGE), and septum, including loss of GAD1 expression. On the other hand, eliminating Gsx1 function from the Dlx1/2 mutants (Dlx1/2;Gsx1 mutants) did not severely exacerbate their phenotype; on the contrary, it resulted in a partial rescue of medial ganglionic eminence (MGE) properties, including interneuron migration to the cortex. Thus, despite their redundant properties, Gsx1 and ‐2 have distinct interactions with Dlx1 and ‐2. Gsx2 interaction is strongest in the LGE, CGE, and septum, whereas the Gsx1 interaction is strongest in the MGE. From these studies, and earlier studies, we present a model of the transcriptional network that regulates early steps of subcortical development. J. Comp. Neurol. 521:1561–1584, 2013. © 2012 Wiley Periodicals, Inc.
Dlx1/2 mutant mice have deficits in subpallial differentiation, including overexpression of Gsx1 and Gsx2. To investigate whether Gsx overexpression contributes to the Dlx1/2−/− phenotypes, we made compound loss‐of‐function mutants. Gsx2;Dlx1/2 mutants showed partial rescue of the increased expression of Notch‐signaling mediators. On the other hand, Gsx1;Dlx1/2 mutants resulted in a partial rescue of interneuron migration to the cortex. Thus, despite their redundant properties, Gsx1 and Gsx2 have distinct interactions with Dlx1 and 2.</abstract><cop>Hoboken</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><pmid>23042297</pmid><doi>10.1002/cne.23242</doi><tpages>24</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Wiley Online Library Journals Frontfile Complete |
| subjects | Animals ASCL1 protein basal ganglia Brain - embryology Brain - physiology CGE development Dlx Embryo, Mammalian Fluorescent Antibody Technique GABA Gsx Homeodomain Proteins - genetics Homeodomain Proteins - metabolism In Situ Hybridization interneuron LGE MGE Mice Mice, Mutant Strains mutant Neurogenesis - physiology Phenotype septum Transcription Factors - genetics |
| title | Loss of Gsx1 and Gsx2 function rescues distinct phenotypes in Dlx1/2 mutants |
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