Expression of all Wnt genes and their secreted antagonists during mouse blastocyst and postimplantation development

Abstract

In this extensive study, real-time reverse transcriptase-polymerase chain reaction was used to analyze the expression levels of all 19 Wnt genes and their 11 potential antagonists in mouse blastocysts, pregastrula, gastrula, and neurula stages. By complementing these results with in situ hybridization, we revealed new expression domains for Wnt2b and Sfrp1, respectively, in the future primitive streak at the posterior side and in the anterior visceral endoderm before the initiation of gastrulation. Moreover, the anterior visceral endoderm expresses three secreted Wnt antagonists (Sfrp1, Sfrp5, and Dkk1) in partially overlapping domains. We also identified expression patterns for the Wnt1, Wnt3a, Wnt6, Wnt7b, Wnt9a, Wnt10b, and Sfrp1 genes at the blastocyst stage. In particular, the expression of Wnt1 and Sfrp1 predominantly in the inner cell mass and of Wnt9a in the mural trophoblast and inner cell mass cells surrounding the blastocoele suggests new roles for the Wnt pathway in preimplantation development. This article is the first report on the regional expression of Wnt genes in the mouse blastocyst.

Sfrp5 coordinates foregut specification and morphogenesis by antagonizing both canonical and noncanonical Wnt11 signaling

“…In the gastrula, candidate antagonists include secreted frizzled-related protein 1 (Sfrp1), Sfrp2, Sfrp3 (Frzb1), Sfrp5, Crescent, and Dkk1, all of which are expressed in the anterior mesendoderm (Leyns et al 1997;Glinka et al 1998;Pilcher and Krieg 2002;Finley et al 2003;Kemp et al 2005). Sfrps sequester Wnt ligands in the extracellular space, preventing them from binding to Frizzled receptors, and thus can inhibit both canonical and noncanonical signaling (Kawano and Kypta 2003).…”

“…In contrast, Dkk1 specifically inhibits the canonical Wnt pathway by binding to LRP6 (Mao et al 2001;Semenov et al 2001). To date, the genetic analysis of Wnt antagonists in the mouse has not revealed a function in foregut development; however, their overlapping expression patterns suggest extensive redundancy (Leimeister et al 1998;Finley et al 2003;Kemp et al 2005). Indeed, mutations in dkk1, sfrp1, sfrp2, or sfrp5, as well as various double and triple mutants, indicate that they have redundant roles in axial trunk formation, but foregut defects have not yet been described in these embryos (Mukhopadhyay et al 2001;Leaf et al 2006;Satoh et al 2006Satoh et al , 2008.…”

Loss of procollagen IIA from the anterior mesendoderm disrupts the development of mouse embryonic forebrain

“…AME expresses signaling ligands such as SHH (Shimamura and Rubenstein, 1997;Gunhaga et al, 2000) and BMP7 (Furuta et al, 1997), and modulators of signaling activity including CHRD, NOG, CER-BERUS, and DKK1 (Biben et al, 1998;Belo et al, 2000;Anderson et al, 2002;Kemp et al, 2005) which act synergistically to regulate the temporal-spatial activity of signaling pathways for forebrain induction and patterning (Dale et al, 1997(Dale et al, , 1999del Barco Barrantes et al, 2003). We have shown that deficiency of IIA in mice results in loss of expression of Shh in the prechordal plate and reduced Six3 and Pax2 expression in the forebrain, and phenocopies the malformation of the prosencephalon and mid-facial structures of the Shhnull mutant (Chiang et al, 1996).…”

The role of Wnt signaling members in the uterus and embryo during pre-implantation and implantation

“…Wnt7b was also shown to be another potential FZD ligand at this stage of development and to be expressed throughout the blastocyst [67]. However, Wnt7b expression was restricted to the extraembryonic region of the forming egg cylinder at implantation, 4.75 dpc [8] Among Wnt ligands expressed in the mouse blastocyst (e.g., Wnts 4, 5b, 7b, 10b, 1, 5a, 7a, 11, and 13), a number of them are newly detectable in the blastocysts (Wnt 1, 5a, 7a, 11, and 13).…”