A.M. Holland,
L.C. Harrison
Pdx1
is a homeobox transcription factor critical for normal pancreatic development.
Using engineered mice in which we can switch off the expression of Pdx1
by doxycycline administration, combined with microarray-based gene expression
analysis, we found that repression of Pdx1 leads to upregulation
of several genes previously implicated in beta-cell regeneration. Importantly,
we also identified a number of differentially expressed genes not previously
known to be associated with beta-cell regeneration. The Pdx1 mouse is
a novel model in which to study genes required for beta-cell regeneration.
We are characterising these genes with a view to developing cell-based
therapies for diabetes.
Laminin-1
and epidermal growth factor family members co-stimulate fetal pancreas
cell proliferation and colony formation
F.-X. Jiang,
L.C.Harrison
The epidermal growth factor
(EGF) family is implicated in the development and function of multiple
cells and organs, including the pancreas. We used a serum-free, low
cell-density culture system to investigate the effect of EGFs on fetal
pancreas cells. EGF receptors ErbB 1,2 and 3 were detected by RT-PCR,
in the developing mouse pancreas between E13.5 and E17.5, and ErbB4
at E17.5. In the presence of the basement membrane glycoprotein, laminin-1,
betacellulin, EGF, transforming growth factor alpha, heparin binding
EGF and epiregulin each induced E15.5 pancreatic cells to proliferate
and form cystoid and solid colonies. These results indicate that laminin-1
and EGF signalling pathways interact to promote pancreas development.
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