Gene array identification of Ipf1/Pdx1-/- regulated genes in pancreatic progenitor cells
1 Umeå Center for Molecular Medicine, Umeå University, SE-901 87 Umeå, Sweden
2 School of Biotechnology, KTH, Royal Institute of Technology, AlbaNova University Center, SE-10691 Stockholm, Sweden
3 Department of Biosciences at Novum, Karolinska Institutet, 14157 Huddinge, Sweden
4 Department of Mathematics and Mathematical Statistics, Umeå University, SE-901 87 Umeå, Sweden Department of Clinical Bacteriology, Universityhospital, SE-90185 Umeå, Sweden
5 Betagenon AB, Box 7966, SE-907 19 Umeå, Sweden
BMC Developmental Biology 2007, 7:129 doi:10.1186/1471-213X-7-129Published: 23 November 2007
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 β-cells leads to impaired β-cell function and diabetes. Although several putative target genes have been linked to the β-cell function of Ipf1/Pdx1, relatively little is known with respect to genes regulated by IPF1/PDX1 in early pancreatic progenitor cells.
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.
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.