Misexpression of the pancreatic homeodomain protein IDX-1 by the Hoxa-4 promoter associated with agenesis of the cecum
Background & Aims: The endoderm-specific homeodomain transcription factor IDX-1 is critical for pancreas development and for the regulation of islet cell–specific genes. During development, IDX-1 is expressed in the epithelial cells of the endoderm in the pancreatic anlage of the foregut. The ai...
Gespeichert in:
| Veröffentlicht in: | Gastroenterology (New York, N.Y. 1943) N.Y. 1943), 1998-08, Vol.115 (2), p.381-387 |
|---|---|
| Hauptverfasser: | , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 387 |
|---|---|
| container_issue | 2 |
| container_start_page | 381 |
| container_title | Gastroenterology (New York, N.Y. 1943) |
| container_volume | 115 |
| creator | Heller, R.Scott Stoffers, Doris A. Hussain, Mehboob A. Miller, Christopher P. Habener, Joel F. |
| description | Background & Aims: The endoderm-specific homeodomain transcription factor IDX-1 is critical for pancreas development and for the regulation of islet cell–specific genes. During development, IDX-1 is expressed in the epithelial cells of the endoderm in the pancreatic anlage of the foregut. The aim of this study was to determine whether IDX-1 may have potential properties of a master homeotic determinant of pancreas and/or gut development.
Methods: Transgenic mice were generated in which the expression of IDX-1 was misdirected by a promoter of the mesoderm-specific homeodomain protein
Hoxa-4 known to express in the stomach and hindgut during development. The expectation was the formation of ectopic pancreatic tissue or alterations of gut patterning or morphology.
Results: Although no ectopic induction of pancreatic markers was found in these transgenic mice, they manifested an altered midgut-hindgut union and agenesis of the cecum. Further, IDX-1 binds to the gut-specific homeodomain protein Cdx-2 and inhibits transactivation of the sucrase-isomaltase promoter by Cdx-2.
Conclusions: These findings further support the emerging understanding that interactions among different classes of homeodomain proteins, expressed in a spatially and temporally restricted manner during development, determine the pattern of organogenesis. A possible mechanism for the dysmorphogenesis of the proximal colon may be an inhibition of Cdx-2 actions by IDX-1.
GASTROENTEROLOGY 1998;115:381-387 |
| doi_str_mv | 10.1016/S0016-5085(98)70204-5 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_80035551</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0016508598702045</els_id><sourcerecordid>80035551</sourcerecordid><originalsourceid>FETCH-LOGICAL-c436t-b36d38aa202031c69c94192edb24bcd1331fcf02fd8b2d2f9d99e339ae8ba1623</originalsourceid><addsrcrecordid>eNqFkElvFDEQRq0IFIaQnxDJB4Tg0MRrj31CKCyJlIgDIHGz3HY1YzTdHlw9Wf59PEvmmovr8L0qVz1Czjj7yBlvz3-y-jaaGf3emg9zJphq9BGZcS1MUzPxgswOyCvyGvEfY8xKw4_JsW3nlik5I7c3CeF-VQAx5ZHmnk4LoCs_hgJ-SoEu8gA55sGnka5KnqDWqy9_Gk67hy17me99ozbZUNNCPWIOyU8Q6V2aFtT_hREw4dPsAGE9vCEve79EON3XE_L729dfF5fN9Y_vVxefr5ugZDs1nWyjNN6Lep3kobXBKm4FxE6oLkQuJe9Dz0QfTSei6G20FqS0HkzneSvkCXm3m1vX-78GnNyQMMBy6UfIa3SGMam15hXUOzCUjFigd6uSBl8eHGdu49ttfbuNTGeN2_p2uvad7T9YdwPEQ9decM3f7nOPwS_7Us0mPGBCKjXnqmKfdhhUGbcJisOQYAwQU4EwuZjTM4s8Am5unT4</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>80035551</pqid></control><display><type>article</type><title>Misexpression of the pancreatic homeodomain protein IDX-1 by the Hoxa-4 promoter associated with agenesis of the cecum</title><source>MEDLINE</source><source>Elsevier ScienceDirect Journals</source><source>Alma/SFX Local Collection</source><creator>Heller, R.Scott ; Stoffers, Doris A. ; Hussain, Mehboob A. ; Miller, Christopher P. ; Habener, Joel F.</creator><creatorcontrib>Heller, R.Scott ; Stoffers, Doris A. ; Hussain, Mehboob A. ; Miller, Christopher P. ; Habener, Joel F.</creatorcontrib><description>Background & Aims: The endoderm-specific homeodomain transcription factor IDX-1 is critical for pancreas development and for the regulation of islet cell–specific genes. During development, IDX-1 is expressed in the epithelial cells of the endoderm in the pancreatic anlage of the foregut. The aim of this study was to determine whether IDX-1 may have potential properties of a master homeotic determinant of pancreas and/or gut development.
Methods: Transgenic mice were generated in which the expression of IDX-1 was misdirected by a promoter of the mesoderm-specific homeodomain protein
Hoxa-4 known to express in the stomach and hindgut during development. The expectation was the formation of ectopic pancreatic tissue or alterations of gut patterning or morphology.
Results: Although no ectopic induction of pancreatic markers was found in these transgenic mice, they manifested an altered midgut-hindgut union and agenesis of the cecum. Further, IDX-1 binds to the gut-specific homeodomain protein Cdx-2 and inhibits transactivation of the sucrase-isomaltase promoter by Cdx-2.
Conclusions: These findings further support the emerging understanding that interactions among different classes of homeodomain proteins, expressed in a spatially and temporally restricted manner during development, determine the pattern of organogenesis. A possible mechanism for the dysmorphogenesis of the proximal colon may be an inhibition of Cdx-2 actions by IDX-1.
GASTROENTEROLOGY 1998;115:381-387</description><identifier>ISSN: 0016-5085</identifier><identifier>EISSN: 1528-0012</identifier><identifier>DOI: 10.1016/S0016-5085(98)70204-5</identifier><identifier>PMID: 9679043</identifier><identifier>CODEN: GASTAB</identifier><language>eng</language><publisher>New York, NY: Elsevier Inc</publisher><subject>Animals ; Biological and medical sciences ; CDX2 Transcription Factor ; Cecum - abnormalities ; Colon - pathology ; DNA-Binding Proteins ; Gastroenterology. Liver. Pancreas. Abdomen ; Gene Expression - physiology ; Homeodomain Proteins - genetics ; Homeodomain Proteins - metabolism ; Homeodomain Proteins - physiology ; Intestinal Mucosa - pathology ; Medical sciences ; Mice ; Mice, Transgenic - genetics ; Oligo-1,6-Glucosidase - genetics ; Other diseases. Semiology ; Promoter Regions, Genetic - physiology ; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus ; Sucrase - genetics ; Trans-Activators - genetics ; Trans-Activators - metabolism ; Transcription, Genetic - physiology</subject><ispartof>Gastroenterology (New York, N.Y. 1943), 1998-08, Vol.115 (2), p.381-387</ispartof><rights>1998 American Gastroenterological Association</rights><rights>1998 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c436t-b36d38aa202031c69c94192edb24bcd1331fcf02fd8b2d2f9d99e339ae8ba1623</citedby><cites>FETCH-LOGICAL-c436t-b36d38aa202031c69c94192edb24bcd1331fcf02fd8b2d2f9d99e339ae8ba1623</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0016508598702045$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=2344714$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9679043$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Heller, R.Scott</creatorcontrib><creatorcontrib>Stoffers, Doris A.</creatorcontrib><creatorcontrib>Hussain, Mehboob A.</creatorcontrib><creatorcontrib>Miller, Christopher P.</creatorcontrib><creatorcontrib>Habener, Joel F.</creatorcontrib><title>Misexpression of the pancreatic homeodomain protein IDX-1 by the Hoxa-4 promoter associated with agenesis of the cecum</title><title>Gastroenterology (New York, N.Y. 1943)</title><addtitle>Gastroenterology</addtitle><description>Background & Aims: The endoderm-specific homeodomain transcription factor IDX-1 is critical for pancreas development and for the regulation of islet cell–specific genes. During development, IDX-1 is expressed in the epithelial cells of the endoderm in the pancreatic anlage of the foregut. The aim of this study was to determine whether IDX-1 may have potential properties of a master homeotic determinant of pancreas and/or gut development.
Methods: Transgenic mice were generated in which the expression of IDX-1 was misdirected by a promoter of the mesoderm-specific homeodomain protein
Hoxa-4 known to express in the stomach and hindgut during development. The expectation was the formation of ectopic pancreatic tissue or alterations of gut patterning or morphology.
Results: Although no ectopic induction of pancreatic markers was found in these transgenic mice, they manifested an altered midgut-hindgut union and agenesis of the cecum. Further, IDX-1 binds to the gut-specific homeodomain protein Cdx-2 and inhibits transactivation of the sucrase-isomaltase promoter by Cdx-2.
Conclusions: These findings further support the emerging understanding that interactions among different classes of homeodomain proteins, expressed in a spatially and temporally restricted manner during development, determine the pattern of organogenesis. A possible mechanism for the dysmorphogenesis of the proximal colon may be an inhibition of Cdx-2 actions by IDX-1.
GASTROENTEROLOGY 1998;115:381-387</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>CDX2 Transcription Factor</subject><subject>Cecum - abnormalities</subject><subject>Colon - pathology</subject><subject>DNA-Binding Proteins</subject><subject>Gastroenterology. Liver. Pancreas. Abdomen</subject><subject>Gene Expression - physiology</subject><subject>Homeodomain Proteins - genetics</subject><subject>Homeodomain Proteins - metabolism</subject><subject>Homeodomain Proteins - physiology</subject><subject>Intestinal Mucosa - pathology</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Transgenic - genetics</subject><subject>Oligo-1,6-Glucosidase - genetics</subject><subject>Other diseases. Semiology</subject><subject>Promoter Regions, Genetic - physiology</subject><subject>Stomach. Duodenum. Small intestine. Colon. Rectum. Anus</subject><subject>Sucrase - genetics</subject><subject>Trans-Activators - genetics</subject><subject>Trans-Activators - metabolism</subject><subject>Transcription, Genetic - physiology</subject><issn>0016-5085</issn><issn>1528-0012</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1998</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkElvFDEQRq0IFIaQnxDJB4Tg0MRrj31CKCyJlIgDIHGz3HY1YzTdHlw9Wf59PEvmmovr8L0qVz1Czjj7yBlvz3-y-jaaGf3emg9zJphq9BGZcS1MUzPxgswOyCvyGvEfY8xKw4_JsW3nlik5I7c3CeF-VQAx5ZHmnk4LoCs_hgJ-SoEu8gA55sGnka5KnqDWqy9_Gk67hy17me99ozbZUNNCPWIOyU8Q6V2aFtT_hREw4dPsAGE9vCEve79EON3XE_L729dfF5fN9Y_vVxefr5ugZDs1nWyjNN6Lep3kobXBKm4FxE6oLkQuJe9Dz0QfTSei6G20FqS0HkzneSvkCXm3m1vX-78GnNyQMMBy6UfIa3SGMam15hXUOzCUjFigd6uSBl8eHGdu49ttfbuNTGeN2_p2uvad7T9YdwPEQ9decM3f7nOPwS_7Us0mPGBCKjXnqmKfdhhUGbcJisOQYAwQU4EwuZjTM4s8Am5unT4</recordid><startdate>19980801</startdate><enddate>19980801</enddate><creator>Heller, R.Scott</creator><creator>Stoffers, Doris A.</creator><creator>Hussain, Mehboob A.</creator><creator>Miller, Christopher P.</creator><creator>Habener, Joel F.</creator><general>Elsevier Inc</general><general>Elsevier</general><scope>IQODW</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>7X8</scope></search><sort><creationdate>19980801</creationdate><title>Misexpression of the pancreatic homeodomain protein IDX-1 by the Hoxa-4 promoter associated with agenesis of the cecum</title><author>Heller, R.Scott ; Stoffers, Doris A. ; Hussain, Mehboob A. ; Miller, Christopher P. ; Habener, Joel F.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c436t-b36d38aa202031c69c94192edb24bcd1331fcf02fd8b2d2f9d99e339ae8ba1623</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1998</creationdate><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>CDX2 Transcription Factor</topic><topic>Cecum - abnormalities</topic><topic>Colon - pathology</topic><topic>DNA-Binding Proteins</topic><topic>Gastroenterology. Liver. Pancreas. Abdomen</topic><topic>Gene Expression - physiology</topic><topic>Homeodomain Proteins - genetics</topic><topic>Homeodomain Proteins - metabolism</topic><topic>Homeodomain Proteins - physiology</topic><topic>Intestinal Mucosa - pathology</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Transgenic - genetics</topic><topic>Oligo-1,6-Glucosidase - genetics</topic><topic>Other diseases. Semiology</topic><topic>Promoter Regions, Genetic - physiology</topic><topic>Stomach. Duodenum. Small intestine. Colon. Rectum. Anus</topic><topic>Sucrase - genetics</topic><topic>Trans-Activators - genetics</topic><topic>Trans-Activators - metabolism</topic><topic>Transcription, Genetic - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Heller, R.Scott</creatorcontrib><creatorcontrib>Stoffers, Doris A.</creatorcontrib><creatorcontrib>Hussain, Mehboob A.</creatorcontrib><creatorcontrib>Miller, Christopher P.</creatorcontrib><creatorcontrib>Habener, Joel F.</creatorcontrib><collection>Pascal-Francis</collection><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><jtitle>Gastroenterology (New York, N.Y. 1943)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Heller, R.Scott</au><au>Stoffers, Doris A.</au><au>Hussain, Mehboob A.</au><au>Miller, Christopher P.</au><au>Habener, Joel F.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Misexpression of the pancreatic homeodomain protein IDX-1 by the Hoxa-4 promoter associated with agenesis of the cecum</atitle><jtitle>Gastroenterology (New York, N.Y. 1943)</jtitle><addtitle>Gastroenterology</addtitle><date>1998-08-01</date><risdate>1998</risdate><volume>115</volume><issue>2</issue><spage>381</spage><epage>387</epage><pages>381-387</pages><issn>0016-5085</issn><eissn>1528-0012</eissn><coden>GASTAB</coden><abstract>Background & Aims: The endoderm-specific homeodomain transcription factor IDX-1 is critical for pancreas development and for the regulation of islet cell–specific genes. During development, IDX-1 is expressed in the epithelial cells of the endoderm in the pancreatic anlage of the foregut. The aim of this study was to determine whether IDX-1 may have potential properties of a master homeotic determinant of pancreas and/or gut development.
Methods: Transgenic mice were generated in which the expression of IDX-1 was misdirected by a promoter of the mesoderm-specific homeodomain protein
Hoxa-4 known to express in the stomach and hindgut during development. The expectation was the formation of ectopic pancreatic tissue or alterations of gut patterning or morphology.
Results: Although no ectopic induction of pancreatic markers was found in these transgenic mice, they manifested an altered midgut-hindgut union and agenesis of the cecum. Further, IDX-1 binds to the gut-specific homeodomain protein Cdx-2 and inhibits transactivation of the sucrase-isomaltase promoter by Cdx-2.
Conclusions: These findings further support the emerging understanding that interactions among different classes of homeodomain proteins, expressed in a spatially and temporally restricted manner during development, determine the pattern of organogenesis. A possible mechanism for the dysmorphogenesis of the proximal colon may be an inhibition of Cdx-2 actions by IDX-1.
GASTROENTEROLOGY 1998;115:381-387</abstract><cop>New York, NY</cop><pub>Elsevier Inc</pub><pmid>9679043</pmid><doi>10.1016/S0016-5085(98)70204-5</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0016-5085 |
| ispartof | Gastroenterology (New York, N.Y. 1943), 1998-08, Vol.115 (2), p.381-387 |
| issn | 0016-5085 1528-0012 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_80035551 |
| source | MEDLINE; Elsevier ScienceDirect Journals; Alma/SFX Local Collection |
| subjects | Animals Biological and medical sciences CDX2 Transcription Factor Cecum - abnormalities Colon - pathology DNA-Binding Proteins Gastroenterology. Liver. Pancreas. Abdomen Gene Expression - physiology Homeodomain Proteins - genetics Homeodomain Proteins - metabolism Homeodomain Proteins - physiology Intestinal Mucosa - pathology Medical sciences Mice Mice, Transgenic - genetics Oligo-1,6-Glucosidase - genetics Other diseases. Semiology Promoter Regions, Genetic - physiology Stomach. Duodenum. Small intestine. Colon. Rectum. Anus Sucrase - genetics Trans-Activators - genetics Trans-Activators - metabolism Transcription, Genetic - physiology |
| title | Misexpression of the pancreatic homeodomain protein IDX-1 by the Hoxa-4 promoter associated with agenesis of the cecum |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-02T07%3A23%3A47IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Misexpression%20of%20the%20pancreatic%20homeodomain%20protein%20IDX-1%20by%20the%20Hoxa-4%20promoter%20associated%20with%20agenesis%20of%20the%20cecum&rft.jtitle=Gastroenterology%20(New%20York,%20N.Y.%201943)&rft.au=Heller,%20R.Scott&rft.date=1998-08-01&rft.volume=115&rft.issue=2&rft.spage=381&rft.epage=387&rft.pages=381-387&rft.issn=0016-5085&rft.eissn=1528-0012&rft.coden=GASTAB&rft_id=info:doi/10.1016/S0016-5085(98)70204-5&rft_dat=%3Cproquest_cross%3E80035551%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=80035551&rft_id=info:pmid/9679043&rft_els_id=S0016508598702045&rfr_iscdi=true |