Concerted involvement of Cdx/Hox genes and Wnt signaling in morphogenesis of the caudal neural tube and cloacal derivatives from the posterior growth zone

Abstract

There was an error in the ePress version of Development 138, 3451-3462 published on 13 July 2011.The first names of one of the authors were listed incorrectly. The final print and online versions are correct, and the correct author list appears above.The authors apologise to readers for this mistake.

In Vitro Generation of Neuromesodermal Progenitors Reveals Distinct Roles for Wnt Signalling in the Specification of Spinal Cord and Paraxial Mesoderm Identity

“…In addition however, a set of ∼240 genes appeared uniquely upregulated in NMP cells (Table S1). These included the transcription factors Brachyury , Nkx1.2 (also known as Sax1 ), which is expressed in the stem zone of midgestation embryos [50],[51] Mixl1 [52], Wnt3a and Cdx2 which are expressed in the primitive streak and nascent mesoderm [32],[33]. In addition Follistatin , which plays a key role in neural induction by blocking TGFβ signalling [53] and components of the Fgf signalling pathway, which is implicated in mesoderm induction [16], are upregulated in NMPs (Figure 3C).…”

“…These signals are required for body axis elongation [16] and both Wnt and Fgf signalling have been implicated in mesoderm and neural induction [22],[25]–[31]. In vivo and in vitro evidence has suggested that Wnt signalling is responsible for posteriorising tissue by inducing posterior Hox genes [29],[32],[33]. Together, the data suggest that the generation of posterior neural tissue and paraxial mesoderm proceeds by Wnt and Fgf signalling inducing a neuromesodermal bipotential intermediate.…”

A Gene Regulatory Network Balances Neural and Mesoderm Specification during Vertebrate Trunk Development

“…Mutations in the Cdx genes block the induction of posterior Hox genes and impair axial extension in embryos (Savory et al., 2009, Young et al., 2009, van de Ven et al., 2011, van Rooijen et al., 2012, Amin et al., 2016, Neijts et al., 2016). The truncation of the body axis can be partially rescued by exposure to Wnt or FGF signaling (Young et al., 2009, van Rooijen et al., 2012, van de Ven et al., 2011). Nevertheless, although the induction of Wnt3a , Fgf8 , and T/Bra by Cdx proteins have been implicated in these phenotypes, the severity of morphological defects in mutant embryos has made it difficult to establish the relative importance of target genes and to rule out others.…”

“…These regions express Wnt and FGF ligands (Wilson et al., 2009). Interfering with either signal results in the depletion of NMPs and the premature truncation of the body axis (Takada et al., 1994, Wilson et al., 2009, Yoshikawa et al., 1997, van de Ven et al., 2011). Both Wnt and FGF signaling are implicated in posteriorizing cells by inducing the Cdx transcription factors (TFs) that promote the expression of more posterior Hox genes (van den Akker et al., 2002, Nordstrom et al., 2006, van de Ven et al., 2011, Mazzoni et al., 2013, Neijts et al., 2016, Amin et al., 2016).…”

“…Interfering with either signal results in the depletion of NMPs and the premature truncation of the body axis (Takada et al., 1994, Wilson et al., 2009, Yoshikawa et al., 1997, van de Ven et al., 2011). Both Wnt and FGF signaling are implicated in posteriorizing cells by inducing the Cdx transcription factors (TFs) that promote the expression of more posterior Hox genes (van den Akker et al., 2002, Nordstrom et al., 2006, van de Ven et al., 2011, Mazzoni et al., 2013, Neijts et al., 2016, Amin et al., 2016). Moreover, Wnt signaling is required for the differentiation of NMPs to mesodermal tissue (Martin and Kimelman, 2012, Garriock et al., 2015) and the loss of Wnt3a results in a depletion of mesodermal tissue in both mice and zebrafish (Yoshikawa et al., 1997, Martin and Kimelman, 2008, Garriock et al., 2015).…”