The AP1 transcription factor Fra2 is required for efficient cartilage development
The AP1 transcription factor Fra2 is required for efficient cartilage development
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DOI：
10.1242/dev.01414
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发表时间：
2004-11-01
期刊：
影响因子：
4.6
通讯作者：
Wagner, EF
中科院分区：
文献类型：
--
作者：
Karreth, F;Hoebertz, A;Wagner, EF
Fos相关的AP 1转录因子Fra 2（由Fosl 2编码）在各种上皮细胞以及软骨结构中表达。我们研究了Fra 2在软骨发育中的作用。Fra 2在胚胎和新生儿中的缺乏导致肥大软骨细胞的区域减少，股骨和胫骨生长板中的基质沉积受损，这可能是由于分化为肥大软骨细胞受损。此外，肥大分化和骨化的原始弓的发展椎骨延迟Fra 2缺陷的胚胎。原代Fosl 2（-/-）软骨细胞表现出减少的肥大分化，并且比野生型细胞更长时间地保持在增殖状态。由于缺乏Fra 2的幼崽在出生后不久就死亡，我们产生了携带“floxed”Fosl 2等位基因的小鼠，并将它们与coll 2a 1-Cre小鼠杂交，从而可以研究出生后的软骨发育。coll 2a 1-Cre、Fosl 2（f/f）小鼠在出生后10至25天之间死亡，生长迟缓，并显示出与Fosl 2（-/-）胚胎相似的较小的生长板。此外，这些小鼠患有脊柱后凸样表型，即脊柱的异常弯曲。因此，Fra 2是一种新的转录因子，通过影响软骨细胞分化对骨骼发育很重要。
The Fos-related AP1 transcription factor Fra2 (encoded by Fosl2) is expressed in various epithelial cells as well as in cartilaginous structures. We studied the role of Fra2 in cartilage development. The absence of Fra2 in embryos and newborns leads to reduced zones of hypertrophic chondrocytes and impaired matrix deposition in femoral and tibial growth plates, probably owing to impaired differentiation into hypertrophic chondrocytes. In addition, hypertrophic differentiation and ossification of primordial arches of the developing vertebrae are delayed in Fra2-deficient embryos. Primary Fosl2(-/-) chondrocytes exhibit decreased hypertrophic differentiation and remain in a proliferative state longer than wild-type cells. As pups lacking Fra2 die shortly after birth, we generated mice carrying 'floxed' Fosl2 alleles and crossed them to coll2a1-Cre mice, allowing investigation of postnatal cartilage development. The coll2a1-Cre, Fosl2(f/f) mice die between 10 and 25 days after birth, are growth retarded and display smaller growth plates similar to Fosl2(-/-) embryos. In addition, these mice suffer from a kyphosis-like phenotype, an abnormal bending of the spine. Hence, Fra2 is a novel transcription factor important for skeletogenesis by affecting chondrocyte differentiation.