Different thresholds of Wnt-Frizzled 7 signaling coordinate proliferation, morphogenesis and fate of endoderm progenitor cells

Perinatal Institute, Division of Developmental Biology, Cincinnati Children's Hospital Medical Center and the College of Medicine, University of Cincinnati, Cincinnati OH 45229 USA.
Developmental Biology (Impact Factor: 3.55). 04/2013; 378(1). DOI: 10.1016/j.ydbio.2013.02.024
Source: PubMed


Wnt signaling has multiple dynamic roles during development of the gastrointestinal and respiratory systems. Differential Wnt signaling is thought to be a critical step in Xenopus endoderm patterning such that during late gastrula and early somite stages of embryogenesis, Wnt activity must be suppressed in the anterior to allow the specification of foregut progenitors. However, the foregut endoderm also expresses the Wnt-receptor Frizzled 7 (Fzd7) as well as several Wnt ligands suggesting that the current model may be too simple. In this study, we show that Fzd7 is required to transduce a low level of Wnt signaling that is essential to maintain foregut progenitors. Foregut-specific Fzd7-depletion from the Xenopus foregut resulted in liver and pancreas agenesis. Fzd7-depleted embryos failed to maintain the foregut progenitor marker hhex and exhibited decreased proliferation; in addition the foregut cells were enlarged with a randomized orientation. We show that in the foregut Fzd7 signals via both the Wnt/β-catenin and Wnt/JNK pathways and that different thresholds of Wnt-Fzd7 activity coordinate progenitor cell fate, proliferation and morphogenesis.

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    • "However, in contrast to the role of WNTs after the hepatic progenitors are formed, at early somite stages, WNT antagonizes expression of the transcription factor hematopoietically expressed homeobox (Hhex), which is required for formation of hepatocytes. These studies imply that specific antagonists of WNT signaling, which may include secreted frizzled-related protein 5 (Sfrp5), regulate the threshold of WNT activity in the anterior foregut to allow the endoderm to adopt a hepatic fate (Li et al. 2008; Zhang et al. 2013). Similar results have been obtained using mouse embryos and human embryonic stem cells (hESCs), suggesting that the temporally regulated inhibition of WNT signaling during hepatic specification is evolutionarily conserved (Han et al. 2011). "

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    • "To test the functional relevance of ATP4a in the context of GI tract ciliation, atp4aSplMO was injected vegetally to target the endoderm (Fig. 5O). Although inhibition of endodermal ATP4a function reduced intestinal foxj1 expression (not shown), it also interfered with normal development of the GI tract (Fig. 5O), a phenotype reminiscent of failure in Wnt-dependent specification of the proximal GI tract [21] "
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    ABSTRACT: During gastrulation and neurulation, foxj1 expression requires ATP4a-dependent Wnt/β-catenin signaling for ciliation of the gastrocoel roof plate [17] and the mucociliary epidermis [19] of Xenopus laevis embryos. These data suggested that ATP4a and Wnt/β-catenin signaling regulate foxj1 throughout Xenopus development. Here we analyzed whether foxj1 expression was also ATP4a-dependent in other ciliated tissues of the developing Xenopus embryo and tadpole. We found that in the floor plate of the neural tube ATP4a-dependent canonical Wnt signaling was required for foxj1 expression, downstream of or in parallel to Hedgehog signaling. In the developing tadpole brain, ATP4-function was a prerequisite for the establishment of cerebrospinal fluid flow. Furthermore, we describe foxj1 expression and the presence of multiciliated cells in the developing tadpole gastrointestinal tract. Our work argues for a general requirement of ATP4-dependent Wnt/β-catenin signaling for foxj1 expression and motile ciliogenesis throughout Xenopus development.
    Full-text · Article · Apr 2015
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    • "Recent studies suggest that in some cases, both pathways can be activated in the same cells without resulting in antagonistic effects. For example, Xenopus Wnt5a and Wnt11 jointly activate both branches of the Wnt pathway to promote axis formation (Cha et al., 2008) and gut development (Li et al., 2008; Zhang et al., 2013). The studies described above suggest that, rather than several parallel pathways, the Wnt pathway is a complex molecular network where the cellular context is fundamental to determine which branch is preferentially activated (van Amerongen and Nusse, 2009). "
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    ABSTRACT: Wnts are essential for a multitude of processes during embryonic development and adult homeostasis. The molecular structure of the Wnt pathway is extremely complex, and it keeps growing as new molecular components and novel interactions are uncovered. Recent studies have advanced our understanding on how the diverse molecular outcomes of the Wnt pathway are integrated during organ development, an integration that is also essential, although mechanistically poorly understood, during the formation of the anterior part of the nervous system, the forebrain. Here, I will summarize these findings and discuss their implications for forebrain development. A special emphasis is put on studies performed in the zebrafish since this model system has been instrumental for our current understanding of forebrain patterning. © 2013 Wiley Periodicals, Inc. Develop Neurobiol, 2013.
    Full-text · Article · Aug 2014 · Developmental Neurobiology
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