Inhibition of Wnt/尾-catenin pathway by Dikkopf-1 affects midfacial morphogenesis in chick embryo

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• 作者：Masayoshi Kawakami¹ ; ^{mkawaka@naramed-u.ac.jp" class="auth_mail} ; Hiroaki Okuda² ; ^{okuda@naramed-u.ac.jp" class="auth_mail} ; Kouko Tatsumi² ; ^{radha815@naramed-u.ac.jp" class="auth_mail} ; Tadaaki Kirita¹ ; ^{tkirita@naramed-u.ac.jp" class="auth_mail} ; Akio Wanaka² ; ^{akiow@naramed-u.ac.jp" class="auth_mail}
• 关键词：Dickkopf-1 (Dkk-1) ; Lhx8 ; Wnt/尾-catenin signaling ; Chick embryo ; Craniofacial development
• 刊名：Journal of Bioscience and Bioengineering
• 出版年：June 2014
• 年：2014
• 卷：117
• 期：6
• 页码：664-669
• 全文大小：2181 K

文摘

The development of the vertebrate face is regulated by complex interactions among several signaling pathways. Dickkopf-1 (Dkk-1), an inhibitor of the Wnt/尾-catenin signaling pathway, can affect midfacial morphogenesis. The downstream target genes of the Wnt/尾-catenin signaling pathway in morphogenesis of the developing upper jaw and lip remain unknown. To investigate the functional roles of Wnt/尾-catenin signaling in facial development, we performed a loss-of-function experiment using local implantation of beads soaked with Dkk-1 during lip fusion at the maxillary prominence of chick embryos at stage 22(HH22). Antagonism of Wnt/尾-catenin signaling by Dkk-1 induced deformities of the premaxilla and jugal bone, which are derived from the maxillary mesenchyme. Real-time and semi-quantitative RT-PCR analysis showed the significant reduction of Lhx8, Msx1 and Msx2 expression levels around the beads in the maxillary mesenchyme at 6 and 24 h after bead implantation. Time course experiments in the HH 22 embryos showed the effect of Dkk-1 on Lhx8, Msx1 and Msx2 expression was not significant after 48 h of the treatment. At HH 26 when the fusion of facial primordial started, Dkk-1 application did not exhibit any significant reduction of those genes. Our findings suggested that Dkk-1 regulates maxillary morphogenesis in chick embryos through Lhx8, Msx1 and Msx2 signals. Wnt/尾-catenin signaling is responsible for intrinsic upper jaw development before the lip fusion.