Hypothalamic sonic hedgehog is required for cell specification and proliferation of LHX3/LHX4 pituitary embryonic precursors
Sonic hedgehog (SHH) is an essential morphogenetic signal that dictates cell fate decisions in several developing organs in mammals. data suggest that SHH is required to specify LHX3 /LHX4 Rathke's pouch (RP) progenitor identity. However, studies have failed to reveal such a function, supportin...
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| Veröffentlicht in: | Development (Cambridge) 2017-09, Vol.144 (18), p.3289-3302 |
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| container_title | Development (Cambridge) |
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| creator | Carreno, Gabriela Apps, John R Lodge, Emily J Panousopoulos, Leonidas Haston, Scott Gonzalez-Meljem, Jose Mario Hahn, Heidi Andoniadou, Cynthia L Martinez-Barbera, Juan Pedro |
| description | Sonic hedgehog (SHH) is an essential morphogenetic signal that dictates cell fate decisions in several developing organs in mammals.
data suggest that SHH is required to specify LHX3
/LHX4
Rathke's pouch (RP) progenitor identity. However,
studies have failed to reveal such a function, supporting instead a crucial role for SHH in promoting proliferation of these RP progenitors and for differentiation of pituitary cell types. Here, we have used a genetic approach to demonstrate that activation of the SHH pathway is necessary to induce LHX3
/LHX4
RP identity in mouse embryos. First, we show that conditional deletion of
in the anterior hypothalamus results in a fully penetrant phenotype characterised by a complete arrest of RP development, with lack of
expression in RP epithelium at 9.0 days post coitum (dpc) and total loss of pituitary tissue by 12.5 dpc. Conversely, overactivation of the SHH pathway by conditional deletion of
in RP progenitors leads to severe hyperplasia and enlargement of the Sox2
stem cell compartment by the end of gestation. |
| doi_str_mv | 10.1242/dev.153387 |
| format | Article |
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data suggest that SHH is required to specify LHX3
/LHX4
Rathke's pouch (RP) progenitor identity. However,
studies have failed to reveal such a function, supporting instead a crucial role for SHH in promoting proliferation of these RP progenitors and for differentiation of pituitary cell types. Here, we have used a genetic approach to demonstrate that activation of the SHH pathway is necessary to induce LHX3
/LHX4
RP identity in mouse embryos. First, we show that conditional deletion of
in the anterior hypothalamus results in a fully penetrant phenotype characterised by a complete arrest of RP development, with lack of
expression in RP epithelium at 9.0 days post coitum (dpc) and total loss of pituitary tissue by 12.5 dpc. Conversely, overactivation of the SHH pathway by conditional deletion of
in RP progenitors leads to severe hyperplasia and enlargement of the Sox2
stem cell compartment by the end of gestation.</description><identifier>ISSN: 0950-1991</identifier><identifier>EISSN: 1477-9129</identifier><identifier>DOI: 10.1242/dev.153387</identifier><identifier>PMID: 28807898</identifier><language>eng</language><publisher>England: The Company of Biologists Ltd</publisher><subject>Cell Compartmentation ; Cell Count ; Cell Differentiation ; Cell fate ; Cell Lineage ; Cell Proliferation ; Clonal deletion ; Clone Cells ; Crosses, Genetic ; Ectoderm - embryology ; Ectoderm - metabolism ; Embryo, Mammalian - metabolism ; Endoderm - embryology ; Endoderm - metabolism ; Epithelium ; Epithelium - embryology ; Epithelium - metabolism ; Female ; Gene Expression Regulation, Developmental ; Genotype ; Gestation ; Hedgehog protein ; Hedgehog Proteins - genetics ; Hedgehog Proteins - metabolism ; Humans ; Hyperplasia ; Hypothalamus (anterior) ; Hypothalamus - embryology ; Hypothalamus - metabolism ; LIM-Homeodomain Proteins - metabolism ; Male ; Mutation - genetics ; Pituitary ; Pituitary Gland - embryology ; Pituitary Gland - metabolism ; Pituitary Gland - pathology ; Signal Transduction ; Stem Cells ; Transcription Factors - metabolism</subject><ispartof>Development (Cambridge), 2017-09, Vol.144 (18), p.3289-3302</ispartof><rights>2017. Published by The Company of Biologists Ltd.</rights><rights>Copyright The Company of Biologists Ltd Sep 15, 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><citedby>FETCH-LOGICAL-c472t-2beaef6a4b097a2271659d99c03d611905d0df4c0c703ec7b58b2cddee3e86843</citedby><cites>FETCH-LOGICAL-c472t-2beaef6a4b097a2271659d99c03d611905d0df4c0c703ec7b58b2cddee3e86843</cites><orcidid>0000-0002-5292-7276 ; 0000-0001-7902-482X ; 0000-0003-4311-5855</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,3665,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28807898$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Carreno, Gabriela</creatorcontrib><creatorcontrib>Apps, John R</creatorcontrib><creatorcontrib>Lodge, Emily J</creatorcontrib><creatorcontrib>Panousopoulos, Leonidas</creatorcontrib><creatorcontrib>Haston, Scott</creatorcontrib><creatorcontrib>Gonzalez-Meljem, Jose Mario</creatorcontrib><creatorcontrib>Hahn, Heidi</creatorcontrib><creatorcontrib>Andoniadou, Cynthia L</creatorcontrib><creatorcontrib>Martinez-Barbera, Juan Pedro</creatorcontrib><title>Hypothalamic sonic hedgehog is required for cell specification and proliferation of LHX3/LHX4 pituitary embryonic precursors</title><title>Development (Cambridge)</title><addtitle>Development</addtitle><description>Sonic hedgehog (SHH) is an essential morphogenetic signal that dictates cell fate decisions in several developing organs in mammals.
data suggest that SHH is required to specify LHX3
/LHX4
Rathke's pouch (RP) progenitor identity. However,
studies have failed to reveal such a function, supporting instead a crucial role for SHH in promoting proliferation of these RP progenitors and for differentiation of pituitary cell types. Here, we have used a genetic approach to demonstrate that activation of the SHH pathway is necessary to induce LHX3
/LHX4
RP identity in mouse embryos. First, we show that conditional deletion of
in the anterior hypothalamus results in a fully penetrant phenotype characterised by a complete arrest of RP development, with lack of
expression in RP epithelium at 9.0 days post coitum (dpc) and total loss of pituitary tissue by 12.5 dpc. Conversely, overactivation of the SHH pathway by conditional deletion of
in RP progenitors leads to severe hyperplasia and enlargement of the Sox2
stem cell compartment by the end of gestation.</description><subject>Cell Compartmentation</subject><subject>Cell Count</subject><subject>Cell Differentiation</subject><subject>Cell fate</subject><subject>Cell Lineage</subject><subject>Cell Proliferation</subject><subject>Clonal deletion</subject><subject>Clone Cells</subject><subject>Crosses, Genetic</subject><subject>Ectoderm - embryology</subject><subject>Ectoderm - metabolism</subject><subject>Embryo, Mammalian - metabolism</subject><subject>Endoderm - embryology</subject><subject>Endoderm - metabolism</subject><subject>Epithelium</subject><subject>Epithelium - embryology</subject><subject>Epithelium - metabolism</subject><subject>Female</subject><subject>Gene Expression Regulation, Developmental</subject><subject>Genotype</subject><subject>Gestation</subject><subject>Hedgehog protein</subject><subject>Hedgehog Proteins - genetics</subject><subject>Hedgehog Proteins - metabolism</subject><subject>Humans</subject><subject>Hyperplasia</subject><subject>Hypothalamus (anterior)</subject><subject>Hypothalamus - embryology</subject><subject>Hypothalamus - metabolism</subject><subject>LIM-Homeodomain Proteins - metabolism</subject><subject>Male</subject><subject>Mutation - genetics</subject><subject>Pituitary</subject><subject>Pituitary Gland - embryology</subject><subject>Pituitary Gland - metabolism</subject><subject>Pituitary Gland - pathology</subject><subject>Signal Transduction</subject><subject>Stem Cells</subject><subject>Transcription Factors - metabolism</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>eNpdkV1LHDEUhoMourW98QeUgDcijOZjZpLcFES0W1joTQu9C5nkzG5kZjImM8KCP96sa8X25gSSh4f35EXojJIrykp27eDpilacS3GAFrQUolCUqUO0IKoiBVWKnqBPKT0QQngtxDE6YVISIZVcoOfldgzTxnSm9xanMOS5AbeGTVhjn3CEx9lHcLgNEVvoOpxGsL711kw-DNgMDo8xdL6FuL8JLV4t__DrPEo8-mn2k4lbDH0Tt6_6MYKdYwoxfUZHrekSfHk7T9Hv-7tft8ti9fP7j9ubVWFLwaaCNWCgrU3ZECUMY4LWlXJKWcJdTakilSOuLS2xgnCwoqlkw6xzABxkLUt-ir7tvePc9OAsDFM0nR6j73M0HYzX_74MfqPX4UlXNWWsqrLg4k0Qw-MMadK9T7vfMAOEOWmqmKKES6Iyev4f-hDmOOT1MiV5SQUTO-HlnrIxpBShfQ9Did6VqnOpel9qhr9-jP-O_m2RvwAItqAl</recordid><startdate>20170915</startdate><enddate>20170915</enddate><creator>Carreno, Gabriela</creator><creator>Apps, John R</creator><creator>Lodge, Emily J</creator><creator>Panousopoulos, Leonidas</creator><creator>Haston, Scott</creator><creator>Gonzalez-Meljem, Jose Mario</creator><creator>Hahn, Heidi</creator><creator>Andoniadou, Cynthia L</creator><creator>Martinez-Barbera, Juan Pedro</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>AAYXX</scope><scope>CITATION</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/0000-0002-5292-7276</orcidid><orcidid>https://orcid.org/0000-0001-7902-482X</orcidid><orcidid>https://orcid.org/0000-0003-4311-5855</orcidid></search><sort><creationdate>20170915</creationdate><title>Hypothalamic sonic hedgehog is required for cell specification and proliferation of LHX3/LHX4 pituitary embryonic precursors</title><author>Carreno, Gabriela ; Apps, John R ; Lodge, Emily J ; Panousopoulos, Leonidas ; Haston, Scott ; Gonzalez-Meljem, Jose Mario ; Hahn, Heidi ; Andoniadou, Cynthia L ; Martinez-Barbera, Juan Pedro</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c472t-2beaef6a4b097a2271659d99c03d611905d0df4c0c703ec7b58b2cddee3e86843</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Cell Compartmentation</topic><topic>Cell Count</topic><topic>Cell Differentiation</topic><topic>Cell fate</topic><topic>Cell Lineage</topic><topic>Cell Proliferation</topic><topic>Clonal deletion</topic><topic>Clone Cells</topic><topic>Crosses, Genetic</topic><topic>Ectoderm - embryology</topic><topic>Ectoderm - metabolism</topic><topic>Embryo, Mammalian - metabolism</topic><topic>Endoderm - embryology</topic><topic>Endoderm - metabolism</topic><topic>Epithelium</topic><topic>Epithelium - embryology</topic><topic>Epithelium - metabolism</topic><topic>Female</topic><topic>Gene Expression Regulation, Developmental</topic><topic>Genotype</topic><topic>Gestation</topic><topic>Hedgehog protein</topic><topic>Hedgehog Proteins - genetics</topic><topic>Hedgehog Proteins - metabolism</topic><topic>Humans</topic><topic>Hyperplasia</topic><topic>Hypothalamus (anterior)</topic><topic>Hypothalamus - embryology</topic><topic>Hypothalamus - metabolism</topic><topic>LIM-Homeodomain Proteins - metabolism</topic><topic>Male</topic><topic>Mutation - genetics</topic><topic>Pituitary</topic><topic>Pituitary Gland - embryology</topic><topic>Pituitary Gland - metabolism</topic><topic>Pituitary Gland - pathology</topic><topic>Signal Transduction</topic><topic>Stem Cells</topic><topic>Transcription Factors - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Carreno, Gabriela</creatorcontrib><creatorcontrib>Apps, John R</creatorcontrib><creatorcontrib>Lodge, Emily J</creatorcontrib><creatorcontrib>Panousopoulos, Leonidas</creatorcontrib><creatorcontrib>Haston, Scott</creatorcontrib><creatorcontrib>Gonzalez-Meljem, Jose Mario</creatorcontrib><creatorcontrib>Hahn, Heidi</creatorcontrib><creatorcontrib>Andoniadou, Cynthia L</creatorcontrib><creatorcontrib>Martinez-Barbera, Juan Pedro</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</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>Carreno, Gabriela</au><au>Apps, John R</au><au>Lodge, Emily J</au><au>Panousopoulos, Leonidas</au><au>Haston, Scott</au><au>Gonzalez-Meljem, Jose Mario</au><au>Hahn, Heidi</au><au>Andoniadou, Cynthia L</au><au>Martinez-Barbera, Juan Pedro</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Hypothalamic sonic hedgehog is required for cell specification and proliferation of LHX3/LHX4 pituitary embryonic precursors</atitle><jtitle>Development (Cambridge)</jtitle><addtitle>Development</addtitle><date>2017-09-15</date><risdate>2017</risdate><volume>144</volume><issue>18</issue><spage>3289</spage><epage>3302</epage><pages>3289-3302</pages><issn>0950-1991</issn><eissn>1477-9129</eissn><abstract>Sonic hedgehog (SHH) is an essential morphogenetic signal that dictates cell fate decisions in several developing organs in mammals.
data suggest that SHH is required to specify LHX3
/LHX4
Rathke's pouch (RP) progenitor identity. However,
studies have failed to reveal such a function, supporting instead a crucial role for SHH in promoting proliferation of these RP progenitors and for differentiation of pituitary cell types. Here, we have used a genetic approach to demonstrate that activation of the SHH pathway is necessary to induce LHX3
/LHX4
RP identity in mouse embryos. First, we show that conditional deletion of
in the anterior hypothalamus results in a fully penetrant phenotype characterised by a complete arrest of RP development, with lack of
expression in RP epithelium at 9.0 days post coitum (dpc) and total loss of pituitary tissue by 12.5 dpc. Conversely, overactivation of the SHH pathway by conditional deletion of
in RP progenitors leads to severe hyperplasia and enlargement of the Sox2
stem cell compartment by the end of gestation.</abstract><cop>England</cop><pub>The Company of Biologists Ltd</pub><pmid>28807898</pmid><doi>10.1242/dev.153387</doi><tpages>14</tpages><orcidid>https://orcid.org/0000-0002-5292-7276</orcidid><orcidid>https://orcid.org/0000-0001-7902-482X</orcidid><orcidid>https://orcid.org/0000-0003-4311-5855</orcidid><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 0950-1991 |
| ispartof | Development (Cambridge), 2017-09, Vol.144 (18), p.3289-3302 |
| issn | 0950-1991 1477-9129 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5612255 |
| source | MEDLINE; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection; Company of Biologists |
| subjects | Cell Compartmentation Cell Count Cell Differentiation Cell fate Cell Lineage Cell Proliferation Clonal deletion Clone Cells Crosses, Genetic Ectoderm - embryology Ectoderm - metabolism Embryo, Mammalian - metabolism Endoderm - embryology Endoderm - metabolism Epithelium Epithelium - embryology Epithelium - metabolism Female Gene Expression Regulation, Developmental Genotype Gestation Hedgehog protein Hedgehog Proteins - genetics Hedgehog Proteins - metabolism Humans Hyperplasia Hypothalamus (anterior) Hypothalamus - embryology Hypothalamus - metabolism LIM-Homeodomain Proteins - metabolism Male Mutation - genetics Pituitary Pituitary Gland - embryology Pituitary Gland - metabolism Pituitary Gland - pathology Signal Transduction Stem Cells Transcription Factors - metabolism |
| title | Hypothalamic sonic hedgehog is required for cell specification and proliferation of LHX3/LHX4 pituitary embryonic precursors |
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