Distinct populations within Isl1 lineages contribute to appendicular and facial skeletogenesis through the β-catenin pathway.
Distinct populations within Isl1 lineages contribute to appendicular and facial skeletogenesis through the β-catenin pathway.
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DOI：
10.1016/j.ydbio.2014.01.001
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发表时间：
2014-03-01
影响因子：
2.7
通讯作者：
Kawakami, Yasuhiko
中科院分区：
文献类型：
--
作者：
Akiyama, Ryutaro;Kawakami, Hiroko;Taketo, M. Mark;Evans, Sylvia M.;Wada, Naoyuki;Petryk, Anna;Kawakami, Yasuhiko
Isl1 expression marks progenitor populations in developing embryos. In this study, we investigated the contribution of Isl1-expressing cells that utilize the β-catenin pathway to skeletal development. Inactivation of β-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 of β-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 β-catenin accumulation and loss of Fgf8 expression in mandibular epithelium of Isl1−/− embryos. Inactivating β-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-> β-catenin-> Fgf8 pathway that regulates mesenchymal survival and development of the lower jaw in the mandibular epithelium. By contrast, activating β-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-β-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.
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影响因子：
2.7
作者：
Joeng KS;Schumacher CA;Zylstra-Diegel CR;Long F;Williams BO
通讯作者：
Williams BO
影响因子：
4.6
作者：
Cohen, Ethan David;Miller, Mayumi F.;Morrisey, Edward E.
通讯作者：
Morrisey, Edward E.
影响因子：
2.6
作者：
Gross, Joshua B.;Hanken, James
通讯作者：
Hanken, James
影响因子：
4.6
作者：
Hill, TP;Taketo, MM;Hartmann, C
通讯作者：
Hartmann, C
DOI：
10.1073/pnas.1121236109
发表时间：
2012-07-03
影响因子：
11.1
作者：
Klaus, Alexandra;Mueller, Marion;Birchmeier, Walter
通讯作者：
Birchmeier, Walter