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

Lanying Song, Yunhong Li, Kai Wang, Ya Zhou Wang, Andrei Molotkov, Lifang Gao, Tianyu Zhao, Takashi Yamagami, Yongping Wang, Qini Gan, David E Pleasure, Chengji Zhou

Research output: Contribution to journalArticle

89 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)3161-3171
Number of pages11
JournalDevelopment
Volume136
Issue number18
DOIs
StatePublished - 2009

Fingerprint

Lip
Wnt Signaling Pathway
Catenins
Cleft Lip
Tretinoin
Homeobox Genes
Gene Fusion
Cleft Palate
Morphogenesis
Embryonic Structures
Enzymes

Keywords

  • Cleft lip
  • Lip morphogenesis
  • Lrp6
  • Mouse
  • Msx
  • Retinoic acid
  • Wnt

ASJC Scopus subject areas

  • Developmental Biology
  • Molecular Biology

Cite this

Song, L., Li, Y., Wang, K., Wang, Y. Z., Molotkov, A., Gao, L., ... Zhou, C. (2009). Lrp6-mediated canonical Wnt signaling is required for lip formation and fusion. Development, 136(18), 3161-3171. https://doi.org/10.1242/dev.037440

Lrp6-mediated canonical Wnt signaling is required for lip formation and fusion. / Song, Lanying; Li, Yunhong; Wang, Kai; Wang, Ya Zhou; Molotkov, Andrei; Gao, Lifang; Zhao, Tianyu; Yamagami, Takashi; Wang, Yongping; Gan, Qini; Pleasure, David E; Zhou, Chengji.

In: Development, Vol. 136, No. 18, 2009, p. 3161-3171.

Research output: Contribution to journalArticle

Song, L, Li, Y, Wang, K, Wang, YZ, Molotkov, A, Gao, L, Zhao, T, Yamagami, T, Wang, Y, Gan, Q, Pleasure, DE & Zhou, C 2009, 'Lrp6-mediated canonical Wnt signaling is required for lip formation and fusion', Development, vol. 136, no. 18, pp. 3161-3171. https://doi.org/10.1242/dev.037440
Song L, Li Y, Wang K, Wang YZ, Molotkov A, Gao L et al. Lrp6-mediated canonical Wnt signaling is required for lip formation and fusion. Development. 2009;136(18):3161-3171. https://doi.org/10.1242/dev.037440
Song, Lanying ; Li, Yunhong ; Wang, Kai ; Wang, Ya Zhou ; Molotkov, Andrei ; Gao, Lifang ; Zhao, Tianyu ; Yamagami, Takashi ; Wang, Yongping ; Gan, Qini ; Pleasure, David E ; Zhou, Chengji. / Lrp6-mediated canonical Wnt signaling is required for lip formation and fusion. In: Development. 2009 ; Vol. 136, No. 18. pp. 3161-3171.
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