Pitx3 and En1 determine the size and molecular programming of the dopaminergic neuronal pool
Mesodiencephalic dopaminergic (mdDA) neurons are located in the ventral midbrain. These neurons form the substantia nigra (SNc) and the ventral tegmental area (VTA). Two transcription factors that play important roles in the process of terminal differentiation and subset-specification of mdDA neuron...
Gespeichert in:
| Veröffentlicht in: | PloS one 2017-08, Vol.12 (8), p.e0182421-e0182421 |
|---|---|
| Hauptverfasser: | , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | e0182421 |
|---|---|
| container_issue | 8 |
| container_start_page | e0182421 |
| container_title | PloS one |
| container_volume | 12 |
| creator | Kouwenhoven, Willemieke M von Oerthel, Lars Smidt, Marten P |
| description | Mesodiencephalic dopaminergic (mdDA) neurons are located in the ventral midbrain. These neurons form the substantia nigra (SNc) and the ventral tegmental area (VTA). Two transcription factors that play important roles in the process of terminal differentiation and subset-specification of mdDA neurons, are paired-like homeodomain transcription factor 3 (Pitx3), and homeobox transcription factor Engrailed 1 (En1). We previously investigated the single Pitx3KO and En1KO and observed important changes in the survival of mdDA neurons of the SNc and VTA as well as altered expression of pivotal rostral- and caudal-markers, Ahd2 and Cck, respectively. To refine our understanding of the regional-specific relationships between En1 and Pitx3 and their (combined) role in the programming mdDA neurons on the rostral-to-caudal axis, we created double En1tm1Alj/tm1Alj;Pitx3gfp/gfp (En1KO;Pitx3GFP/GFP) animals. Here we report, that in absence of En1 and Pitx3, only a limited number of mdDA neurons are present at E14.5. These mdDA neurons have a rudimentary dopaminergic cell fate, as they express Nurr1, Pbx3 and Otx2 but have lost their rostral or caudal subset identity. Furthermore, we report that the expression of Cck depends on En1 expression, while (in contrast) both Pitx3 and En1 are involved in the initiation of Ahd2 expression. Thus we reveal in this manuscript that regulated levels of Pitx3 and En1 control the size and rostral/caudal-identity of the mdDA neuronal population. |
| doi_str_mv | 10.1371/journal.pone.0182421 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_plos_</sourceid><recordid>TN_cdi_plos_journals_1927973111</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A500323259</galeid><doaj_id>oai_doaj_org_article_8fc3ccd6736e421fbc2a20e069a89f4b</doaj_id><sourcerecordid>A500323259</sourcerecordid><originalsourceid>FETCH-LOGICAL-c692t-b9716bfb5edd300685e8cc85421e5a434280206d366406e0207533b115eac4483</originalsourceid><addsrcrecordid>eNqNk12L1DAUhoso7of-A9GCIHoxYz6aNL0RlmXVgYUVv66EkKannQxp001a2fXXm5npLlPZC8lFQvK8b845yUmSFxgtMc3x-40bfafssncdLBEWJCP4UXKMC0oWnCD6-GB9lJyEsEGIUcH50-SICIEQx-w4-fXFDDc0VV2VXnQ4rWAA35oO0mENaTB_YHfUOgt6tMqnvXeNV21EmtTVO6pyvdpKfGN02sHoXQwr7Z2zz5IntbIBnk_zafLj48X388-Ly6tPq_Ozy4XmBRkWZZFjXtYlg6qiMS7BQGgtWEwImMpoRgQiiFeU8wxxiOucUVpizEDpLBP0NHm19-2tC3IqTJC4IHmRU4xxJFZ7onJqI3tvWuVvpVNG7jacb6Tyg9EWpKg11briOeUQI6hLTRRBgHihRFFnZfT6MN02li1UGrrBKzsznZ90Zi0b91syFuuPSTR4Oxl4dz1CGGRrggZrVQdu3MUtGGYC84i-_gd9OLuJalRMwHS1i_fqrak8YwhRQgkrIrV8gIqjgtbo-ItqE_dngnczQWQGuBkaNYYgV9--_j979XPOvjlg16DssA7OjoNxXZiD2R7U3oXgob4vMkZy2wR31ZDbJpBTE0TZy8MHuhfd_Xr6F8gq_-o</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1927973111</pqid></control><display><type>article</type><title>Pitx3 and En1 determine the size and molecular programming of the dopaminergic neuronal pool</title><source>PLoS</source><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>PubMed Central</source><source>Free Full-Text Journals in Chemistry</source><source>EZB Electronic Journals Library</source><creator>Kouwenhoven, Willemieke M ; von Oerthel, Lars ; Smidt, Marten P</creator><contributor>Zhou, Renping</contributor><creatorcontrib>Kouwenhoven, Willemieke M ; von Oerthel, Lars ; Smidt, Marten P ; Zhou, Renping</creatorcontrib><description>Mesodiencephalic dopaminergic (mdDA) neurons are located in the ventral midbrain. These neurons form the substantia nigra (SNc) and the ventral tegmental area (VTA). Two transcription factors that play important roles in the process of terminal differentiation and subset-specification of mdDA neurons, are paired-like homeodomain transcription factor 3 (Pitx3), and homeobox transcription factor Engrailed 1 (En1). We previously investigated the single Pitx3KO and En1KO and observed important changes in the survival of mdDA neurons of the SNc and VTA as well as altered expression of pivotal rostral- and caudal-markers, Ahd2 and Cck, respectively. To refine our understanding of the regional-specific relationships between En1 and Pitx3 and their (combined) role in the programming mdDA neurons on the rostral-to-caudal axis, we created double En1tm1Alj/tm1Alj;Pitx3gfp/gfp (En1KO;Pitx3GFP/GFP) animals. Here we report, that in absence of En1 and Pitx3, only a limited number of mdDA neurons are present at E14.5. These mdDA neurons have a rudimentary dopaminergic cell fate, as they express Nurr1, Pbx3 and Otx2 but have lost their rostral or caudal subset identity. Furthermore, we report that the expression of Cck depends on En1 expression, while (in contrast) both Pitx3 and En1 are involved in the initiation of Ahd2 expression. Thus we reveal in this manuscript that regulated levels of Pitx3 and En1 control the size and rostral/caudal-identity of the mdDA neuronal population.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0182421</identifier><identifier>PMID: 28800615</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Animals ; Biology and Life Sciences ; Breeding ; Cell fate ; Cell Survival ; Cellular Reprogramming ; Cholecystokinin ; Differentiation ; Dopamine ; Dopamine receptors ; Dopaminergic Neurons - cytology ; Dopaminergic Neurons - metabolism ; Embryo, Mammalian - metabolism ; Female ; Green Fluorescent Proteins - metabolism ; Homeobox ; Homeobox genes ; Homeodomain Proteins - metabolism ; Life sciences ; Male ; Medicine and Health Sciences ; Mesencephalon ; Mesencephalon - cytology ; Metabolism ; Mice ; Mutation - genetics ; Neurons ; Nuclear receptors ; Nurr1 protein ; Otx2 protein ; Polymerase Chain Reaction ; Rodents ; Studies ; Substantia nigra ; Transcription factors ; Transcription Factors - metabolism ; Tyrosine 3-Monooxygenase - metabolism ; Ventral tegmentum</subject><ispartof>PloS one, 2017-08, Vol.12 (8), p.e0182421-e0182421</ispartof><rights>COPYRIGHT 2017 Public Library of Science</rights><rights>2017 Kouwenhoven et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2017 Kouwenhoven et al 2017 Kouwenhoven et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-b9716bfb5edd300685e8cc85421e5a434280206d366406e0207533b115eac4483</citedby><cites>FETCH-LOGICAL-c692t-b9716bfb5edd300685e8cc85421e5a434280206d366406e0207533b115eac4483</cites><orcidid>0000-0002-8815-747X</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/PMC5553812/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5553812/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2100,2926,23865,27923,27924,53790,53792,79371,79372</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28800615$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Zhou, Renping</contributor><creatorcontrib>Kouwenhoven, Willemieke M</creatorcontrib><creatorcontrib>von Oerthel, Lars</creatorcontrib><creatorcontrib>Smidt, Marten P</creatorcontrib><title>Pitx3 and En1 determine the size and molecular programming of the dopaminergic neuronal pool</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Mesodiencephalic dopaminergic (mdDA) neurons are located in the ventral midbrain. These neurons form the substantia nigra (SNc) and the ventral tegmental area (VTA). Two transcription factors that play important roles in the process of terminal differentiation and subset-specification of mdDA neurons, are paired-like homeodomain transcription factor 3 (Pitx3), and homeobox transcription factor Engrailed 1 (En1). We previously investigated the single Pitx3KO and En1KO and observed important changes in the survival of mdDA neurons of the SNc and VTA as well as altered expression of pivotal rostral- and caudal-markers, Ahd2 and Cck, respectively. To refine our understanding of the regional-specific relationships between En1 and Pitx3 and their (combined) role in the programming mdDA neurons on the rostral-to-caudal axis, we created double En1tm1Alj/tm1Alj;Pitx3gfp/gfp (En1KO;Pitx3GFP/GFP) animals. Here we report, that in absence of En1 and Pitx3, only a limited number of mdDA neurons are present at E14.5. These mdDA neurons have a rudimentary dopaminergic cell fate, as they express Nurr1, Pbx3 and Otx2 but have lost their rostral or caudal subset identity. Furthermore, we report that the expression of Cck depends on En1 expression, while (in contrast) both Pitx3 and En1 are involved in the initiation of Ahd2 expression. Thus we reveal in this manuscript that regulated levels of Pitx3 and En1 control the size and rostral/caudal-identity of the mdDA neuronal population.</description><subject>Animals</subject><subject>Biology and Life Sciences</subject><subject>Breeding</subject><subject>Cell fate</subject><subject>Cell Survival</subject><subject>Cellular Reprogramming</subject><subject>Cholecystokinin</subject><subject>Differentiation</subject><subject>Dopamine</subject><subject>Dopamine receptors</subject><subject>Dopaminergic Neurons - cytology</subject><subject>Dopaminergic Neurons - metabolism</subject><subject>Embryo, Mammalian - metabolism</subject><subject>Female</subject><subject>Green Fluorescent Proteins - metabolism</subject><subject>Homeobox</subject><subject>Homeobox genes</subject><subject>Homeodomain Proteins - metabolism</subject><subject>Life sciences</subject><subject>Male</subject><subject>Medicine and Health Sciences</subject><subject>Mesencephalon</subject><subject>Mesencephalon - cytology</subject><subject>Metabolism</subject><subject>Mice</subject><subject>Mutation - genetics</subject><subject>Neurons</subject><subject>Nuclear receptors</subject><subject>Nurr1 protein</subject><subject>Otx2 protein</subject><subject>Polymerase Chain Reaction</subject><subject>Rodents</subject><subject>Studies</subject><subject>Substantia nigra</subject><subject>Transcription factors</subject><subject>Transcription Factors - metabolism</subject><subject>Tyrosine 3-Monooxygenase - metabolism</subject><subject>Ventral tegmentum</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNk12L1DAUhoso7of-A9GCIHoxYz6aNL0RlmXVgYUVv66EkKannQxp001a2fXXm5npLlPZC8lFQvK8b845yUmSFxgtMc3x-40bfafssncdLBEWJCP4UXKMC0oWnCD6-GB9lJyEsEGIUcH50-SICIEQx-w4-fXFDDc0VV2VXnQ4rWAA35oO0mENaTB_YHfUOgt6tMqnvXeNV21EmtTVO6pyvdpKfGN02sHoXQwr7Z2zz5IntbIBnk_zafLj48X388-Ly6tPq_Ozy4XmBRkWZZFjXtYlg6qiMS7BQGgtWEwImMpoRgQiiFeU8wxxiOucUVpizEDpLBP0NHm19-2tC3IqTJC4IHmRU4xxJFZ7onJqI3tvWuVvpVNG7jacb6Tyg9EWpKg11briOeUQI6hLTRRBgHihRFFnZfT6MN02li1UGrrBKzsznZ90Zi0b91syFuuPSTR4Oxl4dz1CGGRrggZrVQdu3MUtGGYC84i-_gd9OLuJalRMwHS1i_fqrak8YwhRQgkrIrV8gIqjgtbo-ItqE_dngnczQWQGuBkaNYYgV9--_j979XPOvjlg16DssA7OjoNxXZiD2R7U3oXgob4vMkZy2wR31ZDbJpBTE0TZy8MHuhfd_Xr6F8gq_-o</recordid><startdate>20170811</startdate><enddate>20170811</enddate><creator>Kouwenhoven, Willemieke M</creator><creator>von Oerthel, Lars</creator><creator>Smidt, Marten P</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0002-8815-747X</orcidid></search><sort><creationdate>20170811</creationdate><title>Pitx3 and En1 determine the size and molecular programming of the dopaminergic neuronal pool</title><author>Kouwenhoven, Willemieke M ; von Oerthel, Lars ; Smidt, Marten P</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-b9716bfb5edd300685e8cc85421e5a434280206d366406e0207533b115eac4483</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Animals</topic><topic>Biology and Life Sciences</topic><topic>Breeding</topic><topic>Cell fate</topic><topic>Cell Survival</topic><topic>Cellular Reprogramming</topic><topic>Cholecystokinin</topic><topic>Differentiation</topic><topic>Dopamine</topic><topic>Dopamine receptors</topic><topic>Dopaminergic Neurons - cytology</topic><topic>Dopaminergic Neurons - metabolism</topic><topic>Embryo, Mammalian - metabolism</topic><topic>Female</topic><topic>Green Fluorescent Proteins - metabolism</topic><topic>Homeobox</topic><topic>Homeobox genes</topic><topic>Homeodomain Proteins - metabolism</topic><topic>Life sciences</topic><topic>Male</topic><topic>Medicine and Health Sciences</topic><topic>Mesencephalon</topic><topic>Mesencephalon - cytology</topic><topic>Metabolism</topic><topic>Mice</topic><topic>Mutation - genetics</topic><topic>Neurons</topic><topic>Nuclear receptors</topic><topic>Nurr1 protein</topic><topic>Otx2 protein</topic><topic>Polymerase Chain Reaction</topic><topic>Rodents</topic><topic>Studies</topic><topic>Substantia nigra</topic><topic>Transcription factors</topic><topic>Transcription Factors - metabolism</topic><topic>Tyrosine 3-Monooxygenase - metabolism</topic><topic>Ventral tegmentum</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kouwenhoven, Willemieke M</creatorcontrib><creatorcontrib>von Oerthel, Lars</creatorcontrib><creatorcontrib>Smidt, Marten 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>Opposing Viewpoints Resource Center</collection><collection>Science (Gale in Context)</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database (ProQuest)</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection (Proquest)</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database (Proquest)</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>https://resources.nclive.org/materials</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>ProQuest Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kouwenhoven, Willemieke M</au><au>von Oerthel, Lars</au><au>Smidt, Marten P</au><au>Zhou, Renping</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Pitx3 and En1 determine the size and molecular programming of the dopaminergic neuronal pool</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2017-08-11</date><risdate>2017</risdate><volume>12</volume><issue>8</issue><spage>e0182421</spage><epage>e0182421</epage><pages>e0182421-e0182421</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Mesodiencephalic dopaminergic (mdDA) neurons are located in the ventral midbrain. These neurons form the substantia nigra (SNc) and the ventral tegmental area (VTA). Two transcription factors that play important roles in the process of terminal differentiation and subset-specification of mdDA neurons, are paired-like homeodomain transcription factor 3 (Pitx3), and homeobox transcription factor Engrailed 1 (En1). We previously investigated the single Pitx3KO and En1KO and observed important changes in the survival of mdDA neurons of the SNc and VTA as well as altered expression of pivotal rostral- and caudal-markers, Ahd2 and Cck, respectively. To refine our understanding of the regional-specific relationships between En1 and Pitx3 and their (combined) role in the programming mdDA neurons on the rostral-to-caudal axis, we created double En1tm1Alj/tm1Alj;Pitx3gfp/gfp (En1KO;Pitx3GFP/GFP) animals. Here we report, that in absence of En1 and Pitx3, only a limited number of mdDA neurons are present at E14.5. These mdDA neurons have a rudimentary dopaminergic cell fate, as they express Nurr1, Pbx3 and Otx2 but have lost their rostral or caudal subset identity. Furthermore, we report that the expression of Cck depends on En1 expression, while (in contrast) both Pitx3 and En1 are involved in the initiation of Ahd2 expression. Thus we reveal in this manuscript that regulated levels of Pitx3 and En1 control the size and rostral/caudal-identity of the mdDA neuronal population.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>28800615</pmid><doi>10.1371/journal.pone.0182421</doi><tpages>e0182421</tpages><orcidid>https://orcid.org/0000-0002-8815-747X</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2017-08, Vol.12 (8), p.e0182421-e0182421 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1927973111 |
| source | PLoS; MEDLINE; DOAJ Directory of Open Access Journals; PubMed Central; Free Full-Text Journals in Chemistry; EZB Electronic Journals Library |
| subjects | Animals Biology and Life Sciences Breeding Cell fate Cell Survival Cellular Reprogramming Cholecystokinin Differentiation Dopamine Dopamine receptors Dopaminergic Neurons - cytology Dopaminergic Neurons - metabolism Embryo, Mammalian - metabolism Female Green Fluorescent Proteins - metabolism Homeobox Homeobox genes Homeodomain Proteins - metabolism Life sciences Male Medicine and Health Sciences Mesencephalon Mesencephalon - cytology Metabolism Mice Mutation - genetics Neurons Nuclear receptors Nurr1 protein Otx2 protein Polymerase Chain Reaction Rodents Studies Substantia nigra Transcription factors Transcription Factors - metabolism Tyrosine 3-Monooxygenase - metabolism Ventral tegmentum |
| title | Pitx3 and En1 determine the size and molecular programming of the dopaminergic neuronal pool |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-10T19%3A30%3A25IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Pitx3%20and%20En1%20determine%20the%20size%20and%20molecular%20programming%20of%20the%20dopaminergic%20neuronal%20pool&rft.jtitle=PloS%20one&rft.au=Kouwenhoven,%20Willemieke%20M&rft.date=2017-08-11&rft.volume=12&rft.issue=8&rft.spage=e0182421&rft.epage=e0182421&rft.pages=e0182421-e0182421&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0182421&rft_dat=%3Cgale_plos_%3EA500323259%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1927973111&rft_id=info:pmid/28800615&rft_galeid=A500323259&rft_doaj_id=oai_doaj_org_article_8fc3ccd6736e421fbc2a20e069a89f4b&rfr_iscdi=true |