Fig. 7: Expression of BrafV600E and BrafQ241R leads to abnormal cell lineage specification with increase in TPit (corticotrophs and melanotrophs) and decrease in Pit1 (somatotrops, thyrotrophs and lactotrophs). | Nature Communications

Fig. 7: Expression of BrafV600E and BrafQ241R leads to abnormal cell lineage specification with increase in TPit (corticotrophs and melanotrophs) and decrease in Pit1 (somatotrops, thyrotrophs and lactotrophs).

From: Activating mutations in BRAF disrupt the hypothalamo-pituitary axis leading to hypopituitarism in mice and humans

Fig. 7: Expression of BrafV600E and BrafQ241R leads to abnormal cell lineage specification with increase in TPit (corticotrophs and melanotrophs) and decrease in Pit1 (somatotrops, thyrotrophs and lactotrophs).The alternative text for this image may have been generated using AI.

IHC against TPit (a, d, g), Pit1 (b, e, h) and α-GSU (c, f, i) on sagittal section of E15.5 embryos of Wt (a–c), Prop1:Cre;BrafV600E/+ (d–f) and CAG:Cre;BrafQ241R/+ (g–i). Expression of TPit was increased in the Prop1:Cre;BrafV600E/+ and CAG:Cre;BrafQ241R/+ pituitaries compared to Wt (arrows in d, g). Quantification of TPit-positive cells shows statistically significant increase in the % of TPit+ve cells in both Prop1:Cre;BrafV600E/+ and CAG:Cre;BrafQ241R/+ pituitaries compared to Wt (j). Severe reduction of Pit1 immunoreactivity was observed in Prop1:Cre;BrafV600E/+ with only few positive foci (arrows in e) compared to Wt (b). Quantification of the Pit1-positive cells revealed a decrease in Pit1 cells in Prop1:Cre;BrafV600E/+ and CAG:Cre;BrafQ241R/+ mutant pituitaries (k). Mild reduction of α-GSU was observed in Prop1:Cre;BrafV600E/+ pituitaries (arrows in f) (l). Note that Prop1:Cre;BrafV600E/+ and CAG:Cre;BrafQ241R/+ pituitary glands exhibited morphological abnormalities with expanded overgrowth and bifurcations of IL (arrowheads d–f and g–i) and overall enlarged size. Quantification of percentage of TPit (j), Pit1 (k) and α-GSU-positive cells (l) (***p < 0.001; **p < 0.01; *p < 0.05 one-way ANOVA, data represented as mean ± SEM from n = 4–5 pituitaries per genotype). AL anterior lobe, IL intermediate lobe, PL posterior lobe, IHC immunohistochemistry. Images are representative of four or five embryos per genotype. Scale bar: i 200 µm.

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