Expression of<i>Wnt9b</i>and activation of canonical Wnt signaling during midfacial morphogenesis in mice

Lan, Yu; Ryan, Rosemary C.; Zhang, Zunyi; Bullard, Steven A.; Bush, Jeffrey O.; Maltby, Kathleen M.; Lidral, Andrew C.; Jiang, Rulang

doi:10.1002/dvdy.20723

Cited by 119 publications

(134 citation statements)

References 56 publications

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“…Wnt3 and Wnt9b are expressed in the orofacial region and may be linked to CLP (Carroll et al, 2005;Lan et al, 2006;Niemann et al, 2004). We observed a restricted expression pattern of Wnt3 in the interface between the lnp, maxp and manp of the control embryos; we found a dramatic reduction of Wnt3 in the same regions of Lrp6-KO mice when detected by in situ hybridization but not when detected by the real-time quantitative PCR (see Fig.…”

Section: Msx1 and Msx2 But Not Bmp4 Were Positively Targeted By The Lmentioning

confidence: 60%

Lrp6-mediated canonical Wnt signaling is required for lip formation and fusion

et al. 2009

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Neither the mechanisms that govern lip morphogenesis nor the cause of cleft lip are well understood. We report that genetic inactivation of Lrp6, a co-receptor of the Wnt/β-catenin signaling pathway, leads to cleft lip with cleft palate. The activity of a Wnt signaling reporter is blocked in the orofacial primordia by Lrp6 deletion in mice. The morphological dynamic that is required for normal lip formation and fusion is disrupted in these mutants. The expression of the homeobox genes Msx1 and Msx2 is dramatically reduced in the mutants, which prevents the outgrowth of orofacial primordia, especially in the fusion site. We further demonstrate that Msx1 and Msx2 (but not their potential regulator Bmp4) are the downstream targets of the Wnt/β-catenin signaling pathway during lip formation and fusion. By contrast, a `fusion-resistant'gene, Raldh3 (also known as Aldh1a3), that encodes a retinoic acid-synthesizing enzyme is ectopically expressed in the upper lip primordia of Lrp6-deficient embryos, indicating a region-specific role of the Wnt/β-catenin signaling pathway in repressing retinoic acid signaling. Thus, the Lrp6-mediated Wnt signaling pathway is required for lip development by orchestrating two distinctively different morphogenetic movements.

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Section: Msx1 and Msx2 But Not Bmp4 Were Positively Targeted By The Lmentioning

confidence: 60%

Lrp6-mediated canonical Wnt signaling is required for lip formation and fusion

et al. 2009

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“…Although Wnt3 can activate canonical signaling (3,(43)(44)(45)(46), in myotubes, Wnt3 regulates AChR clustering through a pathway that requires Rac1. Activation of Rac1 and RhoA correlates with the formation of micro-clusters and full-sized clusters, respectively (11,12,47).…”

Section: Discussionmentioning

confidence: 99%

Wnt signaling promotes AChR aggregation at the neuromuscular synapse in collaboration with agrin

Henríquez

Webb

Bence

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

116

143

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“…We discovered that a number of genes were misexpressed in this region of the face after activating SHH signaling in the brain. We focused on the changes that we observed in the BMP, WNT and FGF signaling pathways owing to their importance for facial development (Ashique et al, 2002;Brugmann et al, 2007;Foppiano et al, 2007;Lan et al, 2006;MacDonald et al, 2004;Richman et al, 1997;Song et al, 2004;Storm et al, 2006;Szabo-Rogers et al, 2008).…”

Section: Relationship Between Brain and Facementioning

confidence: 99%

A SHH-responsive signaling center in the forebrain regulates craniofacial morphogenesis via the facial ectoderm

2009

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Interactions among the forebrain, neural crest and facial ectoderm regulate development of the upper jaw. To examine these interactions, we activated the Sonic hedgehog (SHH) pathway in the brain. Beginning 72 hours after activation of the SHH pathway, growth within the avian frontonasal process (FNP) was exaggerated in lateral regions and impaired in medial regions. This growth pattern is similar to that in mice and superimposed a mammalian-like morphology on the upper jaw. Jaw growth is controlled by signals from the frontonasal ectodermal zone (FEZ), and the divergent morphologies that characterize birds and mammals are accompanied by changes in the FEZ. In chicks there is a single FEZ spanning the FNP, but in mice both median nasal processes have a FEZ. In treated chicks, the FEZ was split into right and left domains that resembled the pattern present in mice. Additionally, we observed that, in the brain, fibroblast growth factor 8 (Fgf8) was downregulated, and signals in or near the nasal pit were altered. Raldh2 expression was expanded, whereas Fgf8, Wnt4, Wnt6 and Zfhx1b were downregulated. However, Wnt9b, and activation of the canonical WNT pathway, were unaltered in treated embryos. At later time points the upper beak was shortened owing to hypoplasia of the skeleton, and this phenotype was reproduced when we blocked the FGF pathway. Thus, the brain establishes multiple signaling centers within the developing upper jaw. Changes in organization of the brain that occur during evolution or as a result of disease can alter these centers and thereby generate morphological variation.

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Expression ofWnt9band activation of canonical Wnt signaling during midfacial morphogenesis in mice

Cited by 119 publications

References 56 publications

Lrp6-mediated canonical Wnt signaling is required for lip formation and fusion

Lrp6-mediated canonical Wnt signaling is required for lip formation and fusion

Wnt signaling promotes AChR aggregation at the neuromuscular synapse in collaboration with agrin

A SHH-responsive signaling center in the forebrain regulates craniofacial morphogenesis via the facial ectoderm

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