Gene array identification of Ipf1/Pdx1-/- regulated genes in pancreatic progenitor cells.
BACKGROUND
The homeodomain transcription factor IPF1/PDX1 exerts a dual role in the pancreas; Ipf1/Pdx1 global null mutants fail to develop a pancreas whereas conditional inactivation of Ipf1/Pdx1 in beta-cells leads to impaired beta-cell function and diabetes. Although several putative target genes have been linked to the beta-cell function of Ipf1/Pdx1, relatively little is known with respect to genes regulated by IPF1/PDX1 in early pancreatic progenitor cells.


RESULTS
Microarray analyses identified a total of 111 genes that were differentially expressed in e10.5 pancreatic buds of Ipf1/Pdx1-/- embryos. The expression of one of these, Spondin 1, which encodes an extracellular matrix protein, has not previously been described in the pancreas. Quantitative real-time RT-PCR analyses and immunohistochemical analyses also revealed that the expression of FgfR2IIIb, that encodes the receptor for FGF10, was down-regulated in Ipf1/Pdx1-/- pancreatic progenitor cells.


CONCLUSIONS
This microarray analysis has identified a number of candidate genes that are differentially expressed in Ipf1/Pdx1-/- pancreatic buds. Several of the differentially expressed genes were known to be important for pancreatic progenitor cell proliferation and differentiation whereas others have not previously been associated with pancreatic development.
Umeå Center for Molecular Medicine, Umeå University, SE-901 87 Umeå, Sweden. per.svensson@ucmm.umu.se
Per
P
Svensson
Cecilia
C
Williams
Joakim
J
Lundeberg
Patrik
P
Rydén
Ingela
I
Bergqvist
Helena
H
Edlund
D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation / Q000235:genetics; D049109:Cell Proliferation; D017931:DNA Primers; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D018398:Homeodomain Proteins / Q000502:physiology*; D017403:In Situ Hybridization; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D010179:Pancreas / Q000166:cytology / Q000378:metabolism*; D011247:Pregnancy; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D015534:Trans-Activators / Q000502:physiology*
D017931:DNA Primers; D018398:Homeodomain Proteins; D015534:Trans-Activators; C084010:pancreatic and duodenal homeobox 1 protein