Identification of members of the Wnt signaling pathway in the embryonic pituitary gland

Abstract

Prop1 is one of several transcription factors important for the development of the pituitary gland. Downstream targets of PROP1 and other critical pituitary transcription factors remain largely unknown. We have generated a partial expression profile of the developing pituitary gland containing over 350 transcripts, using cDNA subtractive hybridization between Prop1(df/df) and wild-type embryonic pituitary gland primordia. Numerous classes of genes including transcription factors, membrane associated molecules, and cell cycle regulators were identified in this study. Of the transcripts, 34% do not have sequence similarity to known genes, but are similar to ESTs, and 4% represent novel sequences. Pituitary gland expression of a number of clones was verified using in situ hybridization. Several members of the Wnt signaling pathway were identified in the developing pituitary gland. The frizzled2 receptor, Apc, beta-catenin, groucho, and a novel isoform of TCF4 (officially named Tcf7l2) were identified in developing pituitary libraries. Three N-terminal alternatively spliced Tcf7l2 isoforms are reported here, each of which lacks a DNA-binding domain. Functional studies indicate that these isoforms can act as endogenous inhibitors of Wnt signaling in some contexts. This is the first report of Tcf7l2 and Fzd2 expression in the developing pituitary. These molecules may be important in mediating Wnt signaling during pituitary ontogeny. We expect other transcripts from these libraries to be involved in pituitary gland development.

A variant in the transcription factor 7-like 2 (TCF7L2) gene is associated with an increased risk of gestational diabetes mellitus

“…A recent report demonstrated that TCF7L2 is expressed in pancreatic beta cells [13]. Thus, by affecting the WNT signalling, the variant could influence the beta cell proliferation (and hence insulin secretion) that normally takes place during pregnancy [33,35]. The effect size for gestational diabetes mellitus conferred by this variant is similar to that reported in patients with type 2 diabetes [12].…”

“…TCF7L2, which maps to chromosome 10q25.3, is a transcription factor belonging to the high mobility group-box transcription factors family [34]. It is involved in the wingless-type MMTV integration site family (WNT) signalling pathway, which is important for the development and growth regulatory mechanisms of the cell [35]. The TCF7L2 rs7903146 variant was originally associated with type 2 diabetes in individuals from Iceland, Denmark and the USA [12].…”

Pituitary stem cell regulation: who is pulling the strings?

“…Knockout of Wnt5a leads to a dysmorphic gland, but endocrine cell specification is almost not affected (Cha et al 2004, Potok et al 2008. FZD2 is also expressed in the RP progenitor cells (E12.5), which renders these cells sensitive to the prevailing WNT ligands (Douglas et al 2001, Potok et al 2008. Wnt4 and Fzd2 continue to be upregulated in the neonatal stem cell compartment as compared to the adult SC-SP, which may be associated with the activated status of these cells during neonatal maturation (Table 1).…”

Transcription factor 7-like 1 is involved in hypothalamo–pituitary axis development in mice and humans

“…In the developing HP axis, this pathway coordinates proliferation of RP progenitors and differentiation of hormone-producing cells (34)(35)(36)(37)(38)(39)(40)(41). TCF7L1 has been shown to play critical roles in maintenance of stem cell pluripotency (42,43), tissue homeostasis of the skin epithelia (44), cell lineage determination during gastrulation (45,46), and brain development in vertebrates (47,48).…”