Distinct populations within Isl1 lineages contribute to appendicular and facial skeletogenesis through the beta-catenin pathway

作者：Akiyama Ryutaro; Kawakami Hiroko; Taketo M Mark; Evans Sylvia M; Wada Naoyuki; Petryk Anna; Kawakami Yasuhiko^*

来源：Developmental Biology, 2014, 387(1): 37-48.

DOI：10.1016/j.ydbio.2014.01.001

• Isl1
• beta-catenin
• Limb
• Branchial arch
• Mandible

Isl/ expression marks progenitor populations in developing embryos. In this study, we investigated the contribution of Isl1-expressing cells that utilize the beta-catenin pathway to skeletal development. Inactivation of beta-catenin in Isl1-expressing cells caused agenesis of the hindlimb skeleton and absence of the lower jaw (agnathia). In the hindlimb, Isl1-lineages broadly contributed to the mesenchyme; however, deletion offi-catenin in the Isl1 -lineage caused cell death only in a discrete posterior domain of nascent hindlimb bud mesenchyme. We found that the loss of posterior mesenchyme, which gives rise to Shh-expressing posterior organizer tissue, caused loss of posterior gene expression and failure to expand chondrogenic precursor cells, leading to severe truncation of the hindlimb. In facial tissues, Isl1-expressing cells broadly contributed to facial epithelium. We found reduced nuclear beta-catenin accumulation and loss of Fgf8 expression in mandibular epithelium of Isl1 embryos. Inactivating beta-catenin in Isl1-expressing epithelium caused both loss of epithelial Fgf8 expression and death of mesenchymal cells in the mandibular arch without affecting epithelial proliferation and survival. These results suggest a Isl1 -%26gt; beta-catenin -%26gt; Fgf8 pathway that regulates mesenchymal survival and development of the lower jaw in the mandibular epithelium. By contrast, activating beta-catenin signaling in Isl1-lineages caused activation of Fgf8 broadly in facial epithelium. Our results provide evidence that, despite its broad contribution to hindlimb mesenchyme and facial epithelium, the Isl1-beta-catenin pathway regulates skeletal development of the hindlimb and lower jaw through discrete populations of cells that give rise to Shh-expressing posterior hindlimb mesenchyme and Fgf8-expressing mandibular epithelium.

• 出版日期2014-3-1