Cultured E8.5 Flk-1−/− mutant foreguts
maintain liver, but not pancreas, progenitors. Immunostaining for HNF4α
at E8.5 shows strong expression in the ventral endodermal lip of the anterior
intestinal portal (AIP) in both wild-type (A) and
Flk-1−/− mutant (B) embryos.
HNF4α is also expressed in the heart (H). On E9.5 the liver field (LvP)
is clearly demarcated by HNF4α staining (E, F, arrowheads). The size of
the field in wild-type embryos (E) is noticeably larger than that of the mutants
(F). Respiratory progenitors (arrows) are present in both wild-type and mutant
embryos, but their number is greatly reduced in the mutants. After 5 days of
culture, explants of wild-type (I, M) and
Flk-1−/− mutant (J, N) foreguts
show a similar expansion of liver precursors, which are identified by the
expression of ALB (I, J) and LIV2 (M, N). Volumetric quantitation of cells
expressing ALB in confocal z-stacks shows no statistical difference between
wild-type and Flk-1−/− mutant
explants (O; p > 0.05, N =11 (wild-type) and 8
(Flk-1−/− mutant)).
Immunostaining of E9.5 wild-type embryos (C) for PDX1 shows strong expression in
both the ventral (VP) and dorsal (DP) pancreatic rudiments. NKX2-1 staining
identifies respiratory progenitors in the lung field (arrow). E9.5
Flk-1−/− mutant embryos stained
for PDX1 also show expression in the pancreatic field (D); the number of NKX2-1
respiratory progenitors (arrow) is substantially less than that seen in
wild-type embryos. Note that PDX1 expression in the mutant VP is equivalent to
that seen in wild-type embryos, while PDX1 expression in the DP is considerably
less than in littermate controls. On E10.5, both dorsal and ventral pancreatic
buds have formed in wild-type embryos (G), but only a ventral pancreatic bud is
seen in Flk-1−/− mutants (H). Note
the complete loss of NKX2-1-positive respiratory progenitors in E10.5 mutants.
Explants of E8.5 wild-type foreguts cultured for 5 days show maintenance of PDX1
expression (K), but PDX1 expression in cultured
Flk-1−/− mutant explants was
never observed (L). Scale bars: A, B, C, D, E, F, I, J, K, L, M, N =100
µm, G and H =300 µm.