Autocrine Platelet-derived Growth Factor-Vascular Endothelial Growth Factor Receptor-related (Pvr) Pathway Activity Controls Intestinal Stem Cell Proliferation in the Adult Drosophila Midgut.
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| Title: | Autocrine Platelet-derived Growth Factor-Vascular Endothelial Growth Factor Receptor-related (Pvr) Pathway Activity Controls Intestinal Stem Cell Proliferation in the Adult Drosophila Midgut. |
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| Authors: | Bond, David1, Foley, Edan1 efoley@ualberta.ca |
| Source: | Journal of Biological Chemistry. 8/10/2012, Vol. 287 Issue 33, p27359-27370. 12p. |
| Subjects: | Platelet-derived growth factor, Cell proliferation, Physiological control systems, Cytokines, Stem cells |
| Abstract: | A dynamic pool of undifferentiated somatic stem cells proliferate and differentiate to replace dead or dying mature cell types and maintain the integrity and function of adult tissues. Intestinal stem cells (ISCs) in the Drosophila posterior midgut are a well established model to study the complex genetic circuitry that governs stem cell homeostasis. Exposure of the intestinal epithelium to environmental toxins results in the expression of cytokines and growth factors that drive the rapid proliferation and differentiation of ISCs. In the absence of stress signals, ISC homeostasis is maintained through intrinsic pathways. In this study, we uncovered the PDGF- and VEGF-receptor related (Pvr) pathway as an essential regulator of ISC homeostasis under unstressed conditions in the posterior midgut. We found that Pvr is coexpressed with its ligand Pvf2 in ISCs and that hyperactivation of the Pvr pathway distorts the ISC developmental program and drives intestinal dysplasia. In contrast, we show that mutant ISCs in the Pvf/Pvr pathway are defective in homeostatic proliferation and differentiation, resulting in a failure to generate mature cell types. Additionally, we determined that extrinsic stress signals generated by enteropathogenic infection are epistatic to the hypoplasia generated in Pvf/Pvr mutants, making the Pvr pathway unique among all previously studied intrinsic pathways. Our findings illuminate an evolutionarily conserved signal transduction pathway with essential roles in metazoan embryonic development and direct involvement in numerous disease states. [ABSTRACT FROM AUTHOR] |
| Copyright of Journal of Biological Chemistry is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) | |
| Database: | Engineering Source |
| FullText | Text: Availability: 0 |
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| Header | DbId: egs DbLabel: Engineering Source An: 79240099 AccessLevel: 6 PubType: Academic Journal PubTypeId: academicJournal PreciseRelevancyScore: 0 |
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| Items | – Name: Title Label: Title Group: Ti Data: Autocrine Platelet-derived Growth Factor-Vascular Endothelial Growth Factor Receptor-related (Pvr) Pathway Activity Controls Intestinal Stem Cell Proliferation in the Adult Drosophila Midgut. – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Bond%2C+David%22">Bond, David</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Foley%2C+Edan%22">Foley, Edan</searchLink><relatesTo>1</relatesTo><i> efoley@ualberta.ca</i> – Name: TitleSource Label: Source Group: Src Data: <searchLink fieldCode="JN" term="%22Journal+of+Biological+Chemistry%22">Journal of Biological Chemistry</searchLink>. 8/10/2012, Vol. 287 Issue 33, p27359-27370. 12p. – Name: Subject Label: Subjects Group: Su Data: <searchLink fieldCode="DE" term="%22Platelet-derived+growth+factor%22">Platelet-derived growth factor</searchLink><br /><searchLink fieldCode="DE" term="%22Cell+proliferation%22">Cell proliferation</searchLink><br /><searchLink fieldCode="DE" term="%22Physiological+control+systems%22">Physiological control systems</searchLink><br /><searchLink fieldCode="DE" term="%22Cytokines%22">Cytokines</searchLink><br /><searchLink fieldCode="DE" term="%22Stem+cells%22">Stem cells</searchLink> – Name: Abstract Label: Abstract Group: Ab Data: A dynamic pool of undifferentiated somatic stem cells proliferate and differentiate to replace dead or dying mature cell types and maintain the integrity and function of adult tissues. Intestinal stem cells (ISCs) in the Drosophila posterior midgut are a well established model to study the complex genetic circuitry that governs stem cell homeostasis. Exposure of the intestinal epithelium to environmental toxins results in the expression of cytokines and growth factors that drive the rapid proliferation and differentiation of ISCs. In the absence of stress signals, ISC homeostasis is maintained through intrinsic pathways. In this study, we uncovered the PDGF- and VEGF-receptor related (Pvr) pathway as an essential regulator of ISC homeostasis under unstressed conditions in the posterior midgut. We found that Pvr is coexpressed with its ligand Pvf2 in ISCs and that hyperactivation of the Pvr pathway distorts the ISC developmental program and drives intestinal dysplasia. In contrast, we show that mutant ISCs in the Pvf/Pvr pathway are defective in homeostatic proliferation and differentiation, resulting in a failure to generate mature cell types. Additionally, we determined that extrinsic stress signals generated by enteropathogenic infection are epistatic to the hypoplasia generated in Pvf/Pvr mutants, making the Pvr pathway unique among all previously studied intrinsic pathways. Our findings illuminate an evolutionarily conserved signal transduction pathway with essential roles in metazoan embryonic development and direct involvement in numerous disease states. [ABSTRACT FROM AUTHOR] – Name: AbstractSuppliedCopyright Label: Group: Ab Data: <i>Copyright of Journal of Biological Chemistry is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.) |
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| RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.1074/jbc.M112.378018 Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 12 StartPage: 27359 Subjects: – SubjectFull: Platelet-derived growth factor Type: general – SubjectFull: Cell proliferation Type: general – SubjectFull: Physiological control systems Type: general – SubjectFull: Cytokines Type: general – SubjectFull: Stem cells Type: general Titles: – TitleFull: Autocrine Platelet-derived Growth Factor-Vascular Endothelial Growth Factor Receptor-related (Pvr) Pathway Activity Controls Intestinal Stem Cell Proliferation in the Adult Drosophila Midgut. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Bond, David – PersonEntity: Name: NameFull: Foley, Edan IsPartOfRelationships: – BibEntity: Dates: – D: 10 M: 08 Text: 8/10/2012 Type: published Y: 2012 Identifiers: – Type: issn-print Value: 00219258 Numbering: – Type: volume Value: 287 – Type: issue Value: 33 Titles: – TitleFull: Journal of Biological Chemistry Type: main |
| ResultId | 1 |
