Fig. 4: Activation of the ERK/MAPK pathway in the anterior pituitary gland (Prop1:Cre;BrafV600E/+) results in defective terminal differentiation of endocrine cells.

a–j Immunohistochemistry against GH, TSH, POMC, PRL and LH in coronal sections through the pituitary gland of Prop1:Cre;BrafV600E/+ (b, d, f, h, j) and Wt (a, c, e, g, i) embryos at E17.5 of gestation. Absence of immunoreactivity for GH, TSH, LH in Prop1:Cre;BrafV600E/+ (b, d, j) mutant pituitaries compared to Prop1+/+;BrafV600E/+ (a, c, i) reveals deficient terminal differentiation. Note that the anterior pituitary in Prop1:Cre;BrafV600E/+ is enlarged compared to Wt littermates. Prop1:Cre;BrafV600E/+ pituitaries exhibit an increase in POMC (f) and PRL (h) expression compared to Wt littermates (e, g, respectively). d′, h′ Higher magnification views of the squared area in d and h, respectively, revealing an expanded intermediate lobe (IL arrowheads in d′ and h′) with multiple bifurcations (arrows in d′ and h′). Images are representative of three embryos per genotype. IL intermediate lobe, PL posterior lobe, GH growth hormone, TSH thyroid-stimulating hormone, POMC proopiomelanocortin, PRL prolactin, LH, luteinising hormone. Scale bar: f, 200 µm; h′ 500 µm.