Regulation of Brn3b by DLX1 and DLX2 is required for retinal ganglion cell differentiation in the vertebrate retina
Regulated retinal ganglion cell (RGC) differentiation and axonal guidance is required for a functional visual system. Homeodomain and basic helix-loop-helix transcription factors are required for retinogenesis, as well as patterning, differentiation and maintenance of specific retinal cell types. We...
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| Veröffentlicht in: | Development (Cambridge) 2017-05, Vol.144 (9), p.1698-1711 |
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| creator | Zhang, Qi Zagozewski, Jamie Cheng, Shaohong Dixit, Rajiv Zhang, Shunzhen de Melo, Jimmy Mu, Xiuqian Klein, William H Brown, Nadean L Wigle, Jeffrey T Schuurmans, Carol Eisenstat, David D |
| description | Regulated retinal ganglion cell (RGC) differentiation and axonal guidance is required for a functional visual system. Homeodomain and basic helix-loop-helix transcription factors are required for retinogenesis, as well as patterning, differentiation and maintenance of specific retinal cell types. We hypothesized that
,
and
homeobox genes function in parallel intrinsic pathways to determine RGC fate and therefore generated
/
/
triple-knockout mice. A more severe retinal phenotype was found in the
/
/
-null retinas than was predicted by combining features of the
single- and
/
double-knockout retinas, including near total RGC loss with a marked increase in amacrine cells in the ganglion cell layer. Furthermore, we discovered that DLX1 and DLX2 function as direct transcriptional activators of
expression. Knockdown of
expression in primary embryonic retinal cultures and
gain of function
strongly support that DLX2 is both necessary and sufficient for
expression
We suggest that ATOH7 specifies RGC-committed progenitors and that
and
function both downstream of ATOH7 and in parallel, but cooperative, pathways that involve regulation of
expression to determine RGC fate. |
| doi_str_mv | 10.1242/dev.142042 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5450843</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1897368052</sourcerecordid><originalsourceid>FETCH-LOGICAL-j429t-80a6fea1140143d65162ae0dd85d40495baf95c50a9bd04ed0b28e52e1885a63</originalsourceid><addsrcrecordid>eNqNkU1r20AQhpeQELtOL_0BZSGXXJTO7Ie0eyk0Tr_AEAg59CZW3pGzRl7ZK8mQfx-ZOKHtKaeZYZ55eWeGsU8I1yiU-OJpf41KgBInbIqqKDKLwp6yKVgNGVqLE_ah69YAIPOiOGcTYaTOJeKUdfe0GhrXhzbytuY3KcqKV0_8dvEHuYv-kAgeOp5oN4REntdtGos-RNfwlYur5jC6pKbhPtQ1JYp9eNELkfePxPeUeqqS6-k4d8HOatd09PEYZ-zhx_eH-a9scffz9_zbIlsrYfvMgMtrcogKUEmfa8yFI_DeaK9AWV252uqlBmcrD4o8VMKQFoTGaJfLGfv6Irsdqg355WgsuabcprBx6alsXSj_7cTwWK7afamVBqPkKHB1FEjtbqCuLzehO2zqIrVDV6KxhcwNaPEO1AgNOB59RC__Q9ftkMZrjpQ1Ugmh4EB9_tv8m-vXz8lnblaZ2A</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1983422403</pqid></control><display><type>article</type><title>Regulation of Brn3b by DLX1 and DLX2 is required for retinal ganglion cell differentiation in the vertebrate retina</title><source>MEDLINE</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Alma/SFX Local Collection</source><source>Company of Biologists</source><creator>Zhang, Qi ; Zagozewski, Jamie ; Cheng, Shaohong ; Dixit, Rajiv ; Zhang, Shunzhen ; de Melo, Jimmy ; Mu, Xiuqian ; Klein, William H ; Brown, Nadean L ; Wigle, Jeffrey T ; Schuurmans, Carol ; Eisenstat, David D</creator><creatorcontrib>Zhang, Qi ; Zagozewski, Jamie ; Cheng, Shaohong ; Dixit, Rajiv ; Zhang, Shunzhen ; de Melo, Jimmy ; Mu, Xiuqian ; Klein, William H ; Brown, Nadean L ; Wigle, Jeffrey T ; Schuurmans, Carol ; Eisenstat, David D</creatorcontrib><description>Regulated retinal ganglion cell (RGC) differentiation and axonal guidance is required for a functional visual system. Homeodomain and basic helix-loop-helix transcription factors are required for retinogenesis, as well as patterning, differentiation and maintenance of specific retinal cell types. We hypothesized that
,
and
homeobox genes function in parallel intrinsic pathways to determine RGC fate and therefore generated
/
/
triple-knockout mice. A more severe retinal phenotype was found in the
/
/
-null retinas than was predicted by combining features of the
single- and
/
double-knockout retinas, including near total RGC loss with a marked increase in amacrine cells in the ganglion cell layer. Furthermore, we discovered that DLX1 and DLX2 function as direct transcriptional activators of
expression. Knockdown of
expression in primary embryonic retinal cultures and
gain of function
strongly support that DLX2 is both necessary and sufficient for
expression
We suggest that ATOH7 specifies RGC-committed progenitors and that
and
function both downstream of ATOH7 and in parallel, but cooperative, pathways that involve regulation of
expression to determine RGC fate.</description><identifier>ISSN: 0950-1991</identifier><identifier>EISSN: 1477-9129</identifier><identifier>DOI: 10.1242/dev.142042</identifier><identifier>PMID: 28356311</identifier><language>eng</language><publisher>England: The Company of Biologists Ltd</publisher><subject>Amacrine cells ; Amacrine Cells - cytology ; Amacrine Cells - metabolism ; Animals ; Apoptosis - genetics ; Axon guidance ; Base Sequence ; Basic Helix-Loop-Helix Transcription Factors - genetics ; Basic Helix-Loop-Helix Transcription Factors - metabolism ; Brn-3 protein ; Cell Count ; Cell Differentiation ; Cell Division - genetics ; Cell Lineage - genetics ; Cell Proliferation ; Cells, Cultured ; Cholinergic Neurons - cytology ; Cholinergic Neurons - metabolism ; Electroporation ; Embryo, Mammalian - cytology ; Embryo, Mammalian - metabolism ; Embryos ; Gene Deletion ; Gene Expression Regulation, Developmental ; Gene Knockdown Techniques ; Helix-loop-helix proteins (basic) ; Homeobox ; Homeodomain Proteins - metabolism ; Mice, Knockout ; Models, Biological ; Nerve Tissue Proteins - genetics ; Nerve Tissue Proteins - metabolism ; Pattern formation ; Promoter Regions, Genetic ; Protein Binding ; Retina ; Retinal ganglion cells ; Retinal Ganglion Cells - cytology ; Retinal Ganglion Cells - metabolism ; Retinogenesis ; RNA, Messenger - genetics ; RNA, Messenger - metabolism ; Transcription Factor Brn-3B - deficiency ; Transcription Factor Brn-3B - metabolism ; Transcription factors ; Transcription Factors - deficiency ; Transcription Factors - metabolism ; Vertebrates - metabolism ; Visual system</subject><ispartof>Development (Cambridge), 2017-05, Vol.144 (9), p.1698-1711</ispartof><rights>2017. Published by The Company of Biologists Ltd.</rights><rights>Copyright The Company of Biologists Ltd May 1, 2017</rights><rights>2017. Published by The Company of Biologists Ltd 2017</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><orcidid>0000-0003-2130-9050 ; 0000-0002-5976-0798</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28356311$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhang, Qi</creatorcontrib><creatorcontrib>Zagozewski, Jamie</creatorcontrib><creatorcontrib>Cheng, Shaohong</creatorcontrib><creatorcontrib>Dixit, Rajiv</creatorcontrib><creatorcontrib>Zhang, Shunzhen</creatorcontrib><creatorcontrib>de Melo, Jimmy</creatorcontrib><creatorcontrib>Mu, Xiuqian</creatorcontrib><creatorcontrib>Klein, William H</creatorcontrib><creatorcontrib>Brown, Nadean L</creatorcontrib><creatorcontrib>Wigle, Jeffrey T</creatorcontrib><creatorcontrib>Schuurmans, Carol</creatorcontrib><creatorcontrib>Eisenstat, David D</creatorcontrib><title>Regulation of Brn3b by DLX1 and DLX2 is required for retinal ganglion cell differentiation in the vertebrate retina</title><title>Development (Cambridge)</title><addtitle>Development</addtitle><description>Regulated retinal ganglion cell (RGC) differentiation and axonal guidance is required for a functional visual system. Homeodomain and basic helix-loop-helix transcription factors are required for retinogenesis, as well as patterning, differentiation and maintenance of specific retinal cell types. We hypothesized that
,
and
homeobox genes function in parallel intrinsic pathways to determine RGC fate and therefore generated
/
/
triple-knockout mice. A more severe retinal phenotype was found in the
/
/
-null retinas than was predicted by combining features of the
single- and
/
double-knockout retinas, including near total RGC loss with a marked increase in amacrine cells in the ganglion cell layer. Furthermore, we discovered that DLX1 and DLX2 function as direct transcriptional activators of
expression. Knockdown of
expression in primary embryonic retinal cultures and
gain of function
strongly support that DLX2 is both necessary and sufficient for
expression
We suggest that ATOH7 specifies RGC-committed progenitors and that
and
function both downstream of ATOH7 and in parallel, but cooperative, pathways that involve regulation of
expression to determine RGC fate.</description><subject>Amacrine cells</subject><subject>Amacrine Cells - cytology</subject><subject>Amacrine Cells - metabolism</subject><subject>Animals</subject><subject>Apoptosis - genetics</subject><subject>Axon guidance</subject><subject>Base Sequence</subject><subject>Basic Helix-Loop-Helix Transcription Factors - genetics</subject><subject>Basic Helix-Loop-Helix Transcription Factors - metabolism</subject><subject>Brn-3 protein</subject><subject>Cell Count</subject><subject>Cell Differentiation</subject><subject>Cell Division - genetics</subject><subject>Cell Lineage - genetics</subject><subject>Cell Proliferation</subject><subject>Cells, Cultured</subject><subject>Cholinergic Neurons - cytology</subject><subject>Cholinergic Neurons - metabolism</subject><subject>Electroporation</subject><subject>Embryo, Mammalian - cytology</subject><subject>Embryo, Mammalian - metabolism</subject><subject>Embryos</subject><subject>Gene Deletion</subject><subject>Gene Expression Regulation, Developmental</subject><subject>Gene Knockdown Techniques</subject><subject>Helix-loop-helix proteins (basic)</subject><subject>Homeobox</subject><subject>Homeodomain Proteins - metabolism</subject><subject>Mice, Knockout</subject><subject>Models, Biological</subject><subject>Nerve Tissue Proteins - genetics</subject><subject>Nerve Tissue Proteins - metabolism</subject><subject>Pattern formation</subject><subject>Promoter Regions, Genetic</subject><subject>Protein Binding</subject><subject>Retina</subject><subject>Retinal ganglion cells</subject><subject>Retinal Ganglion Cells - cytology</subject><subject>Retinal Ganglion Cells - metabolism</subject><subject>Retinogenesis</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Messenger - metabolism</subject><subject>Transcription Factor Brn-3B - deficiency</subject><subject>Transcription Factor Brn-3B - metabolism</subject><subject>Transcription factors</subject><subject>Transcription Factors - deficiency</subject><subject>Transcription Factors - metabolism</subject><subject>Vertebrates - metabolism</subject><subject>Visual system</subject><issn>0950-1991</issn><issn>1477-9129</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkU1r20AQhpeQELtOL_0BZSGXXJTO7Ie0eyk0Tr_AEAg59CZW3pGzRl7ZK8mQfx-ZOKHtKaeZYZ55eWeGsU8I1yiU-OJpf41KgBInbIqqKDKLwp6yKVgNGVqLE_ah69YAIPOiOGcTYaTOJeKUdfe0GhrXhzbytuY3KcqKV0_8dvEHuYv-kAgeOp5oN4REntdtGos-RNfwlYur5jC6pKbhPtQ1JYp9eNELkfePxPeUeqqS6-k4d8HOatd09PEYZ-zhx_eH-a9scffz9_zbIlsrYfvMgMtrcogKUEmfa8yFI_DeaK9AWV252uqlBmcrD4o8VMKQFoTGaJfLGfv6Irsdqg355WgsuabcprBx6alsXSj_7cTwWK7afamVBqPkKHB1FEjtbqCuLzehO2zqIrVDV6KxhcwNaPEO1AgNOB59RC__Q9ftkMZrjpQ1Ugmh4EB9_tv8m-vXz8lnblaZ2A</recordid><startdate>20170501</startdate><enddate>20170501</enddate><creator>Zhang, Qi</creator><creator>Zagozewski, Jamie</creator><creator>Cheng, Shaohong</creator><creator>Dixit, Rajiv</creator><creator>Zhang, Shunzhen</creator><creator>de Melo, Jimmy</creator><creator>Mu, Xiuqian</creator><creator>Klein, William H</creator><creator>Brown, Nadean L</creator><creator>Wigle, Jeffrey T</creator><creator>Schuurmans, Carol</creator><creator>Eisenstat, David D</creator><general>The Company of Biologists Ltd</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7QP</scope><scope>7SS</scope><scope>7TK</scope><scope>7TM</scope><scope>7U9</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-2130-9050</orcidid><orcidid>https://orcid.org/0000-0002-5976-0798</orcidid></search><sort><creationdate>20170501</creationdate><title>Regulation of Brn3b by DLX1 and DLX2 is required for retinal ganglion cell differentiation in the vertebrate retina</title><author>Zhang, Qi ; Zagozewski, Jamie ; Cheng, Shaohong ; Dixit, Rajiv ; Zhang, Shunzhen ; de Melo, Jimmy ; Mu, Xiuqian ; Klein, William H ; Brown, Nadean L ; Wigle, Jeffrey T ; Schuurmans, Carol ; Eisenstat, David D</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-j429t-80a6fea1140143d65162ae0dd85d40495baf95c50a9bd04ed0b28e52e1885a63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Amacrine cells</topic><topic>Amacrine Cells - cytology</topic><topic>Amacrine Cells - metabolism</topic><topic>Animals</topic><topic>Apoptosis - genetics</topic><topic>Axon guidance</topic><topic>Base Sequence</topic><topic>Basic Helix-Loop-Helix Transcription Factors - genetics</topic><topic>Basic Helix-Loop-Helix Transcription Factors - metabolism</topic><topic>Brn-3 protein</topic><topic>Cell Count</topic><topic>Cell Differentiation</topic><topic>Cell Division - genetics</topic><topic>Cell Lineage - genetics</topic><topic>Cell Proliferation</topic><topic>Cells, Cultured</topic><topic>Cholinergic Neurons - cytology</topic><topic>Cholinergic Neurons - metabolism</topic><topic>Electroporation</topic><topic>Embryo, Mammalian - cytology</topic><topic>Embryo, Mammalian - metabolism</topic><topic>Embryos</topic><topic>Gene Deletion</topic><topic>Gene Expression Regulation, Developmental</topic><topic>Gene Knockdown Techniques</topic><topic>Helix-loop-helix proteins (basic)</topic><topic>Homeobox</topic><topic>Homeodomain Proteins - metabolism</topic><topic>Mice, Knockout</topic><topic>Models, Biological</topic><topic>Nerve Tissue Proteins - genetics</topic><topic>Nerve Tissue Proteins - metabolism</topic><topic>Pattern formation</topic><topic>Promoter Regions, Genetic</topic><topic>Protein Binding</topic><topic>Retina</topic><topic>Retinal ganglion cells</topic><topic>Retinal Ganglion Cells - cytology</topic><topic>Retinal Ganglion Cells - metabolism</topic><topic>Retinogenesis</topic><topic>RNA, Messenger - genetics</topic><topic>RNA, Messenger - metabolism</topic><topic>Transcription Factor Brn-3B - deficiency</topic><topic>Transcription Factor Brn-3B - metabolism</topic><topic>Transcription factors</topic><topic>Transcription Factors - deficiency</topic><topic>Transcription Factors - metabolism</topic><topic>Vertebrates - metabolism</topic><topic>Visual system</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhang, Qi</creatorcontrib><creatorcontrib>Zagozewski, Jamie</creatorcontrib><creatorcontrib>Cheng, Shaohong</creatorcontrib><creatorcontrib>Dixit, Rajiv</creatorcontrib><creatorcontrib>Zhang, Shunzhen</creatorcontrib><creatorcontrib>de Melo, Jimmy</creatorcontrib><creatorcontrib>Mu, Xiuqian</creatorcontrib><creatorcontrib>Klein, William H</creatorcontrib><creatorcontrib>Brown, Nadean L</creatorcontrib><creatorcontrib>Wigle, Jeffrey T</creatorcontrib><creatorcontrib>Schuurmans, Carol</creatorcontrib><creatorcontrib>Eisenstat, David D</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Development (Cambridge)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhang, Qi</au><au>Zagozewski, Jamie</au><au>Cheng, Shaohong</au><au>Dixit, Rajiv</au><au>Zhang, Shunzhen</au><au>de Melo, Jimmy</au><au>Mu, Xiuqian</au><au>Klein, William H</au><au>Brown, Nadean L</au><au>Wigle, Jeffrey T</au><au>Schuurmans, Carol</au><au>Eisenstat, David D</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Regulation of Brn3b by DLX1 and DLX2 is required for retinal ganglion cell differentiation in the vertebrate retina</atitle><jtitle>Development (Cambridge)</jtitle><addtitle>Development</addtitle><date>2017-05-01</date><risdate>2017</risdate><volume>144</volume><issue>9</issue><spage>1698</spage><epage>1711</epage><pages>1698-1711</pages><issn>0950-1991</issn><eissn>1477-9129</eissn><abstract>Regulated retinal ganglion cell (RGC) differentiation and axonal guidance is required for a functional visual system. Homeodomain and basic helix-loop-helix transcription factors are required for retinogenesis, as well as patterning, differentiation and maintenance of specific retinal cell types. We hypothesized that
,
and
homeobox genes function in parallel intrinsic pathways to determine RGC fate and therefore generated
/
/
triple-knockout mice. A more severe retinal phenotype was found in the
/
/
-null retinas than was predicted by combining features of the
single- and
/
double-knockout retinas, including near total RGC loss with a marked increase in amacrine cells in the ganglion cell layer. Furthermore, we discovered that DLX1 and DLX2 function as direct transcriptional activators of
expression. Knockdown of
expression in primary embryonic retinal cultures and
gain of function
strongly support that DLX2 is both necessary and sufficient for
expression
We suggest that ATOH7 specifies RGC-committed progenitors and that
and
function both downstream of ATOH7 and in parallel, but cooperative, pathways that involve regulation of
expression to determine RGC fate.</abstract><cop>England</cop><pub>The Company of Biologists Ltd</pub><pmid>28356311</pmid><doi>10.1242/dev.142042</doi><tpages>14</tpages><orcidid>https://orcid.org/0000-0003-2130-9050</orcidid><orcidid>https://orcid.org/0000-0002-5976-0798</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0950-1991 |
| ispartof | Development (Cambridge), 2017-05, Vol.144 (9), p.1698-1711 |
| issn | 0950-1991 1477-9129 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5450843 |
| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection; Company of Biologists |
| subjects | Amacrine cells Amacrine Cells - cytology Amacrine Cells - metabolism Animals Apoptosis - genetics Axon guidance Base Sequence Basic Helix-Loop-Helix Transcription Factors - genetics Basic Helix-Loop-Helix Transcription Factors - metabolism Brn-3 protein Cell Count Cell Differentiation Cell Division - genetics Cell Lineage - genetics Cell Proliferation Cells, Cultured Cholinergic Neurons - cytology Cholinergic Neurons - metabolism Electroporation Embryo, Mammalian - cytology Embryo, Mammalian - metabolism Embryos Gene Deletion Gene Expression Regulation, Developmental Gene Knockdown Techniques Helix-loop-helix proteins (basic) Homeobox Homeodomain Proteins - metabolism Mice, Knockout Models, Biological Nerve Tissue Proteins - genetics Nerve Tissue Proteins - metabolism Pattern formation Promoter Regions, Genetic Protein Binding Retina Retinal ganglion cells Retinal Ganglion Cells - cytology Retinal Ganglion Cells - metabolism Retinogenesis RNA, Messenger - genetics RNA, Messenger - metabolism Transcription Factor Brn-3B - deficiency Transcription Factor Brn-3B - metabolism Transcription factors Transcription Factors - deficiency Transcription Factors - metabolism Vertebrates - metabolism Visual system |
| title | Regulation of Brn3b by DLX1 and DLX2 is required for retinal ganglion cell differentiation in the vertebrate retina |
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