Ofd1 is required in limb bud patterning and endochondral bone development
Ofd1 is required in limb bud patterning and endochondral bone development
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DOI：
10.1016/j.ydbio.2010.09.020
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发表时间：
2011-01-15
影响因子：
2.7
通讯作者：
Franco, Brunella
中科院分区：
文献类型：
--
作者：
Bimonte, Sabrina;De Angelis, Amalia;Franco, Brunella
口腔-面部-数字I型（OFDI）综合征是一种x连锁的男性致命性发育障碍。它被归因于纤毛功能障碍，以面部、口腔和手指畸形为特征。使用不同的Cre系进行条件失活，使我们能够研究Ofd1转录本在肢体发育中的作用。免疫荧光和超微结构研究表明，Ofd1对于肢体芽的纤毛发育是必需的，但对于纤毛的生长却不是必需的，这与之前在胚胎淋巴结中所显示的情况相反。间充质Ofd1失活的突变体表现为严重的多指畸形，丧失前后（A/P）指型和缩短长骨。手指身份的丧失被发现与Shh信号的逐渐丧失和Gli3的加工受损有关，而肢体生长缺陷是由于Ihh信号缺陷和软骨内骨形成过程中的矿化缺陷造成的。我们的数据表明，在肢体和骨骼模式中，Ofd1在调节手指数量和身份方面发挥作用，增加了对初级纤毛在发育过程中的功能作用的认识。(C) 2010爱思唯尔公司版权所有。
Oral-facial-digital type I (OFDI) syndrome is an X-linked male lethal developmental disorder. It is ascribed to ciliary dysfunction and characterized by malformation of the face, oral cavity, and digits. Conditional inactivation using different Cre lines allowed us to study the role of the Ofd1 transcript in limb development. Immunofluorescence and ultrastructural studies showed that Ofd1 is necessary for correct ciliogenesis in the limb bud but not for cilia outgrowth, in contrast to what was previously shown for the embryonic node. Mutants with mesenchymal Ofd1 inactivation display severe polydactyly with loss of antero-posterior (A/P) digit patterning and shortened long bones. Loss of digit identity was found to be associated with a progressive loss of Shh signaling and an impaired processing of Gli3, whereas defects in limb outgrowth were due to defective Ihh signaling and to mineralization defects during endochondral bone formation.Our data demonstrate that Ofd1 plays a role in regulating digit number and identity during limb and skeletal patterning increasing insight on the functional role of primary cilia during development. (C) 2010 Elsevier Inc. All rights reserved.