Wnt3 signaling in the epiblast is required for proper orientation of the anteroposterior axis

Barrow, Jeffery R.; Howell, William D.; Rule, Michael C.; Hayashi, Shigemi; Thomas, Kirk R.; Capecchi, Mario R.; McMahon, Andrew P.

doi:10.1016/j.ydbio.2007.09.030

Cited by 76 publications

(74 citation statements)

References 34 publications

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“…This phenotypic discrepancy suggests that the VE is a transient source of Wnt ligands at E7.5. This finding is supported by a recent study showing that Wnt3 secreted from the VE is sufficient to induce, but not maintain, gastrulation in epiblastspecific Wnt3 mutants (Barrow et al, 2007;Tortelote et al, 2013). In order to determine whether Porcn-dependent Wnt secretion from the VE is also necessary, we generated embryos with Porcn functionally mutant extra-embryonic tissues based on imprinted XCI.…”

Section: Discussionmentioning

confidence: 61%

“…This phenotype appears identical to that of zygotic Wnt3 mutants (Liu et al, 1999), which also fail to initiate gastrulation. In contrast to Porcn mutants, epiblast-specific Wnt3 mutants and Porcn null aggregation embryos initiate gastrulation but fail to maintain it (Barrow et al, 2007;Biechele et al, 2011;Tortelote et al, 2013). These observations suggest that VE-secreted Wnt3 is sufficient to induce the initial phases of gastrulation in Porcn or Wnt3 mutant epiblast, as the extra-embryonic tissues are wild type in both settings.…”

Section: Porcn Mutant Embryos (Porcn Del/ymentioning

confidence: 90%

“…As these embryos have wild-type extraembryonic tissues that can act as sources of Wnt signaling (Barrow et al, 2007;Tortelote et al, 2013), we investigated whether zygotic and epiblast-specific mutants differ in phenotype. We generated zygotic Porcn mutant embryos by deletion with a ubiquitously expressed Cre recombinase (Belteki et al, 2005).…”

Section: In Vitromentioning

confidence: 99%

“…We investigated a potential requirement for Porcn in the VE by a direct approach that was not dependent on XCI, using the previously described VE-specific Ttr::Cre allele (Kwon and Hadjantonakis, 2009 (Barrow et al, 2007;Biechele et al, 2011;Tortelote et al, 2013), these results show that Wnt3 secreted from wild-type VE is sufficient to induce gastrulation in mutant epiblast but may not be required for the induction of gastrulation in wild-type epiblast or can function in the absence of Porcn in the VE. …”

Section: Porcn Is Not Required In the Visceral Endodermmentioning

confidence: 99%

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Porcn-dependent Wnt signaling is not required prior to mouse gastrulation

et al. 2013

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SUMMARYIn mice and humans the X-chromosomal porcupine homolog (Porcn) gene is required for the acylation and secretion of all 19 Wnt ligands and thus represents a bottleneck for all Wnt signaling. We have generated a mouse line carrying a floxed allele for Porcn and used zygotic, oocyte-specific and visceral endoderm-specific deletions to investigate embryonic and extra-embryonic requirements for Wnt ligand secretion. We show that there is no requirement for Porcn-dependent secretion of Wnt ligands during preimplantation development of the mouse embryo. Porcn-dependent Wnts are first required for the initiation of gastrulation, where Porcn function is required in the epiblast but not the visceral endoderm. Heterozygous female embryos, which are mutant in both trophoblast and visceral endoderm due to imprinted X chromosome inactivation, complete gastrulation but display chorio-allantoic fusion defects similar to Wnt7b mutants. Our studies highlight the importance of Wnt3 and Wnt7b for embryonic and placental development but suggest that endogenous Porcn-dependent Wnt secretion does not play an essential role in either implantation or blastocyst lineage specification.

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Section: Discussionmentioning

confidence: 61%

Section: Porcn Mutant Embryos (Porcn Del/ymentioning

confidence: 90%

Section: In Vitromentioning

confidence: 99%

Section: Porcn Is Not Required In the Visceral Endodermmentioning

confidence: 99%

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Porcn-dependent Wnt signaling is not required prior to mouse gastrulation

et al. 2013

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“…In Wnt3 -/-mutants, the primitive streak does not form and gastrulation does not occur (Liu et al 1999;Barrow et al 2007). Almost identical defects are observed when the function of both Lrp5 and -6 are disrupted in Lrp5 -/-; Lrp6 -/-mutants or mesd (mesoderm development) mutants, which lacks a chaperone specifically required for trafficking Lrp5/6 to the plasma membrane (Hsieh et al 2003;Kelly et al 2004).…”

Section: E65mentioning

confidence: 99%