Abstract:
:Joints form within the developing skeleton through the segmentation and cavitation of initially continuous cartilage condensations. However, the molecular pathways controlling joint formation largely remain to be clarified. In particular, while several critical secreted signals have been identified, no transcription factors have yet been described as acting in the early stages of joint formation. Working upstream of the early joint marker Wnt9a, we found that the transcription factor c-Jun plays a pivotal role in specifying joint cell fates. We first identified an enhancer upstream of the Wnt9a gene driving joint-specific expression in transgenic reporter mice. A comprehensive in silico screen suggested c-Jun as a candidate transcription factor activating this Wnt9a enhancer element. c-Jun is specifically expressed in joints during embryonic joint development, and its conditional deletion from early limb bud mesenchyme in mice severely affects both initiation and subsequent differentiation of all limb joints. c-Jun directly regulates Wnt16 as well as Wnt9a during early stages of joint development, causing a decrease of canonical Wnt activity in the joint interzone. Postnatally, c-Jun-deficient mice show a range of joint abnormalities, including cartilaginous continuities between juxtaposed skeletal elements, irregular articular surfaces, and hypoplasia of ligaments.
journal_name
Genes Devjournal_title
Genes & developmentauthors
Kan A,Tabin CJdoi
10.1101/gad.209239.112subject
Has Abstractpub_date
2013-03-01 00:00:00pages
514-24issue
5eissn
0890-9369issn
1549-5477pii
27/5/514journal_volume
27pub_type
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