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Gene expression profiling of a mouse model of pancreatic islet dysmorphogenesis.

Wilding Crawford L, Tweedie Ables E, Oh YA, Boone B, Levy S, Gannon M - PLoS ONE (2008)

Bottom Line: Despite this success, many of the factors necessary for proper islet morphogenesis and function remain uncharacterized.Genome-wide microarray analysis was used to identify differences in the gene expression profiles of late gestation and early postnatal total pancreas tissue from wild type and Hnf6 transgenic animals.This study provides a unique dataset that can act as a starting point for other investigators to explore the role of the identified genes in pancreatogenesis, islet morphogenesis and mature beta cell function.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, Nashville, Tennessee, USA.

ABSTRACT

Background: In the past decade, several transcription factors critical for pancreas organogenesis have been identified. Despite this success, many of the factors necessary for proper islet morphogenesis and function remain uncharacterized. Previous studies have shown that transgenic over-expression of the transcription factor Hnf6 specifically in the pancreatic endocrine cell lineage resulted in disruptions in islet morphogenesis, including dysfunctional endocrine cell sorting, increased individual islet size, increased number of peripheral endocrine cell types, and failure of islets to migrate away from the ductal epithelium. The mechanisms whereby maintained Hnf6 causes defects in islet morphogenesis have yet to be elucidated.

Methodology/principal findings: We exploited the dysmorphic islets in Hnf6 transgenic animals as a tool to identify factors important for islet morphogenesis. Genome-wide microarray analysis was used to identify differences in the gene expression profiles of late gestation and early postnatal total pancreas tissue from wild type and Hnf6 transgenic animals. Here we report the identification of genes with an altered expression in Hnf6 transgenic animals and highlight factors with potential importance in islet morphogenesis. Importantly, gene products involved in cell adhesion, cell migration, ECM remodeling and proliferation were found to be altered in Hnf6 transgenic pancreata, revealing specific candidates that can now be analyzed directly for their role in these processes during islet development.

Conclusions/significance: This study provides a unique dataset that can act as a starting point for other investigators to explore the role of the identified genes in pancreatogenesis, islet morphogenesis and mature beta cell function.

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Related in: MedlinePlus

Relative proportion of transcripts altered in Hnf6 Tg animals as determined by gene ontology analysis.Known transcripts altered by 1.5-fold or greater were placed into one of 16 categories, represented by specific colors on each chart. (A) Transcripts up-regulated at e18.5 (total 582). (B) Transcripts down-regulated at e18.5 (total 283). (C) Transcripts up-regulated at P1 (total 135). (D) Transcripts down-regulated at P1 (total 161).
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pone-0001611-g004: Relative proportion of transcripts altered in Hnf6 Tg animals as determined by gene ontology analysis.Known transcripts altered by 1.5-fold or greater were placed into one of 16 categories, represented by specific colors on each chart. (A) Transcripts up-regulated at e18.5 (total 582). (B) Transcripts down-regulated at e18.5 (total 283). (C) Transcripts up-regulated at P1 (total 135). (D) Transcripts down-regulated at P1 (total 161).

Mentions: Each gene was placed into one of 17 categories, which include: protease/protease inhibitors, enzymes, cell adhesion, cytoskeletal and ECM, signaling molecules, nucleic acid binding proteins, membrane proteins, secreted proteins, vesicle proteins, blood proteins, and cell cycle (Figure 4). Unknown genes were not included in the analysis but comprised less than 40% of up or down-regulated genes at either time point (unknown genes represent a total of 39.5% of the 45,070 probesets on the microarray). Since the completion of our original analysis, some of these previously “unknown” gene products may subsequently have been functionally characterized and ascribed to a particular cellular process. These transcripts are also included in the entire data set and may be obtained at www.vmsr.net/supl/mouse_islet.


Gene expression profiling of a mouse model of pancreatic islet dysmorphogenesis.

Wilding Crawford L, Tweedie Ables E, Oh YA, Boone B, Levy S, Gannon M - PLoS ONE (2008)

Relative proportion of transcripts altered in Hnf6 Tg animals as determined by gene ontology analysis.Known transcripts altered by 1.5-fold or greater were placed into one of 16 categories, represented by specific colors on each chart. (A) Transcripts up-regulated at e18.5 (total 582). (B) Transcripts down-regulated at e18.5 (total 283). (C) Transcripts up-regulated at P1 (total 135). (D) Transcripts down-regulated at P1 (total 161).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2249940&req=5

pone-0001611-g004: Relative proportion of transcripts altered in Hnf6 Tg animals as determined by gene ontology analysis.Known transcripts altered by 1.5-fold or greater were placed into one of 16 categories, represented by specific colors on each chart. (A) Transcripts up-regulated at e18.5 (total 582). (B) Transcripts down-regulated at e18.5 (total 283). (C) Transcripts up-regulated at P1 (total 135). (D) Transcripts down-regulated at P1 (total 161).
Mentions: Each gene was placed into one of 17 categories, which include: protease/protease inhibitors, enzymes, cell adhesion, cytoskeletal and ECM, signaling molecules, nucleic acid binding proteins, membrane proteins, secreted proteins, vesicle proteins, blood proteins, and cell cycle (Figure 4). Unknown genes were not included in the analysis but comprised less than 40% of up or down-regulated genes at either time point (unknown genes represent a total of 39.5% of the 45,070 probesets on the microarray). Since the completion of our original analysis, some of these previously “unknown” gene products may subsequently have been functionally characterized and ascribed to a particular cellular process. These transcripts are also included in the entire data set and may be obtained at www.vmsr.net/supl/mouse_islet.

Bottom Line: Despite this success, many of the factors necessary for proper islet morphogenesis and function remain uncharacterized.Genome-wide microarray analysis was used to identify differences in the gene expression profiles of late gestation and early postnatal total pancreas tissue from wild type and Hnf6 transgenic animals.This study provides a unique dataset that can act as a starting point for other investigators to explore the role of the identified genes in pancreatogenesis, islet morphogenesis and mature beta cell function.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, Nashville, Tennessee, USA.

ABSTRACT

Background: In the past decade, several transcription factors critical for pancreas organogenesis have been identified. Despite this success, many of the factors necessary for proper islet morphogenesis and function remain uncharacterized. Previous studies have shown that transgenic over-expression of the transcription factor Hnf6 specifically in the pancreatic endocrine cell lineage resulted in disruptions in islet morphogenesis, including dysfunctional endocrine cell sorting, increased individual islet size, increased number of peripheral endocrine cell types, and failure of islets to migrate away from the ductal epithelium. The mechanisms whereby maintained Hnf6 causes defects in islet morphogenesis have yet to be elucidated.

Methodology/principal findings: We exploited the dysmorphic islets in Hnf6 transgenic animals as a tool to identify factors important for islet morphogenesis. Genome-wide microarray analysis was used to identify differences in the gene expression profiles of late gestation and early postnatal total pancreas tissue from wild type and Hnf6 transgenic animals. Here we report the identification of genes with an altered expression in Hnf6 transgenic animals and highlight factors with potential importance in islet morphogenesis. Importantly, gene products involved in cell adhesion, cell migration, ECM remodeling and proliferation were found to be altered in Hnf6 transgenic pancreata, revealing specific candidates that can now be analyzed directly for their role in these processes during islet development.

Conclusions/significance: This study provides a unique dataset that can act as a starting point for other investigators to explore the role of the identified genes in pancreatogenesis, islet morphogenesis and mature beta cell function.

Show MeSH
Related in: MedlinePlus