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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

Assessment of replicate consistency and gene expression changes.Each line on the graph represents an individual spot on the array. Normalized ratio values of the average for the three WT samples (WT1-WT3) were plotted against each individual WT sample (left) and each individual Hnf6 Tg sample (right; Tg1-Tg3). Ratio values indicating no change in gene expression are seen in yellow at a value of 1.0. Transcripts that have an altered expression in Hnf6 Tg animals compared to WT animals are indicated in shades of red (greater than 1.0) or blue (less than 1.0).
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pone-0001611-g002: Assessment of replicate consistency and gene expression changes.Each line on the graph represents an individual spot on the array. Normalized ratio values of the average for the three WT samples (WT1-WT3) were plotted against each individual WT sample (left) and each individual Hnf6 Tg sample (right; Tg1-Tg3). Ratio values indicating no change in gene expression are seen in yellow at a value of 1.0. Transcripts that have an altered expression in Hnf6 Tg animals compared to WT animals are indicated in shades of red (greater than 1.0) or blue (less than 1.0).

Mentions: Gene expression ratio values were calculated by comparing signal intensity values for each individual sample to the average signal intensity value of the control or WT triplicates. This allows an assessment of the consistency of the replicates and to compare gene expression levels in WT and Hnf6 Tg pancreas at e18.5 (data not shown) and P1 (Figure 2). Ratio values for all WT samples were highly consistent with little sample-to-sample variability (Figure 2, left). In the Hnf6 Tg samples plot (Figure 2, right), the majority of the genes remained centered around a ratio value of 1.0 (indicating no change in expression); however, there were also subsets of genes with ratio values greater than and less than 1.0, shown in red and blue, respectively. These represent genes that have an altered expression in Hnf6 Tg animals compared to WT animals.


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)

Assessment of replicate consistency and gene expression changes.Each line on the graph represents an individual spot on the array. Normalized ratio values of the average for the three WT samples (WT1-WT3) were plotted against each individual WT sample (left) and each individual Hnf6 Tg sample (right; Tg1-Tg3). Ratio values indicating no change in gene expression are seen in yellow at a value of 1.0. Transcripts that have an altered expression in Hnf6 Tg animals compared to WT animals are indicated in shades of red (greater than 1.0) or blue (less than 1.0).
© Copyright Policy
Related In: Results  -  Collection

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

pone-0001611-g002: Assessment of replicate consistency and gene expression changes.Each line on the graph represents an individual spot on the array. Normalized ratio values of the average for the three WT samples (WT1-WT3) were plotted against each individual WT sample (left) and each individual Hnf6 Tg sample (right; Tg1-Tg3). Ratio values indicating no change in gene expression are seen in yellow at a value of 1.0. Transcripts that have an altered expression in Hnf6 Tg animals compared to WT animals are indicated in shades of red (greater than 1.0) or blue (less than 1.0).
Mentions: Gene expression ratio values were calculated by comparing signal intensity values for each individual sample to the average signal intensity value of the control or WT triplicates. This allows an assessment of the consistency of the replicates and to compare gene expression levels in WT and Hnf6 Tg pancreas at e18.5 (data not shown) and P1 (Figure 2). Ratio values for all WT samples were highly consistent with little sample-to-sample variability (Figure 2, left). In the Hnf6 Tg samples plot (Figure 2, right), the majority of the genes remained centered around a ratio value of 1.0 (indicating no change in expression); however, there were also subsets of genes with ratio values greater than and less than 1.0, shown in red and blue, respectively. These represent genes that have an altered expression in Hnf6 Tg animals compared to WT animals.

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