WNT signaling affects gene expression in the ventral diencephalon and pituitary gland growth

• Published in: Developmental dynamics 2008-04, Vol.237 (4), p.1006-1020
• Main Authors: Potok, Mary Anne, Cha, Kelly B., Hunt, Andrea, Brinkmeier, Michelle L., Leitges, Michael, Kispert, Andreas, Camper, Sally A.
• Format: Article
• Language: English
• Subjects: Animals; Bone Morphogenetic Proteins - genetics; Bone Morphogenetic Proteins - metabolism; Cell Lineage; development; Diencephalon - anatomy & histology; Diencephalon - embryology; Diencephalon - growth & development; Diencephalon - physiology; Female; Fibroblast Growth Factors - genetics; Fibroblast Growth Factors - metabolism; Gene Expression Regulation, Developmental; Mice; Mice, Inbred C57BL; Mice, Knockout; Morphogenesis; mouse knockout; Mutation; Phenotype; Pituitary Gland - anatomy & histology; Pituitary Gland - embryology; Pituitary Gland - growth & development; Pituitary Gland - physiology; Pituitary Hormones - genetics; Pituitary Hormones - metabolism; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins - metabolism; Signal Transduction - physiology; Wnt Proteins - genetics; Wnt Proteins - metabolism; Wnt-5a Protein; Wnt11; Wnt16; Wnt4; Wnt4 Protein; Wnt5a; Wnt6
• ISSN: 1058-8388; 1097-0177
• DOI: 10.1002/dvdy.21511

We examined the role of WNT signaling in pituitary development by characterizing the pituitary phenotype of three WNT knockout mice and assessing the expression of WNT pathway components. Wnt5a mutants have expanded domains of Fgf10 and bone morphogenetic protein expression in the ventral diencephalon and a reduced domain of LHX3 expression in Rathke's pouch. Wnt4 mutants have mildly reduced cell differentiation, reduced POU1F1 expression, and mild anterior lobe hypoplasia. Wnt4, Wnt5a double mutants exhibit an additive pituitary phenotype of dysmorphology and mild hypoplasia. Wnt6 mutants have no obvious pituitary phenotype. We surveyed WNT expression and identified transcripts for numerous Wnts, Frizzleds, and downstream pathway members in the pituitary and ventral diencephalon. These findings support the emerging model that WNT signaling affects the pituitary gland via effects on ventral diencephalon signaling, and suggest additional Wnt genes that are worthy of functional studies. Developmental Dynamics 237:1006–1020, 2008. © 2008 Wiley‐Liss, Inc.