Retinoic acid signaling spatially restricts osteoblasts and controls ray-interray organization during zebrafish fin regeneration
Retinoic acid signaling spatially restricts osteoblasts and controls ray-interray organization during zebrafish fin regeneration
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DOI：
10.1242/dev.120212
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发表时间：
2015-09-01
期刊：
影响因子：
4.6
通讯作者：
Begemann, Gerrit
中科院分区：
文献类型：
--
作者：
Blum, Nicola;Begemann, Gerrit
斑马鱼尾鳍由重复的骨条单位组成，这些骨条被软的骨条间组织分开，该组织必须在鳍再生期间忠实地重建。如何以及为什么再生射线尊重射线间边界，从而只延伸现有的骨骼，仍然没有解决。在这里，我们证明了一个维甲酸（RA）降解的小生境是由Cyp26a1在近端基底表皮层，编排射线interray组织空间限制成骨细胞。破坏这个小生境导致前成骨细胞忽略射线间边界，并侵入相邻的射线间，在那里它们形成异位骨。同时，非成骨细胞芽基细胞和再生血管扩散到间鳍条中，导致鳍条间鳍条组织的整体破坏和鳍再生的不可逆抑制。表达cyp26a1的小生境在随后的再生生长过程中起着另一个重要作用，它促进了Shha促进的成骨细胞增殖。最后，我们表明，以前观察到的远端移位的射线分叉再生鳍后，RA治疗或截肢接近分叉可以解释不适当的preosteoblast对齐，并不一定需要推定的proximodistal信息的变化。我们的研究结果揭示了一种机制，调节前成骨细胞对齐和维护射线间的边界在鳍再生。
The zebrafish caudal fin consists of repeated units of bony rays separated by soft interray tissue, an organization that must be faithfully re-established during fin regeneration. How and why regenerating rays respect ray-interray boundaries, thus extending only the existing bone, has remained unresolved. Here, we demonstrate that a retinoic acid (RA)-degrading niche is established by Cyp26a1 in the proximal basal epidermal layer that orchestrates ray-interray organization by spatially restricting osteoblasts. Disruption of this niche causes preosteoblasts to ignore ray-interray boundaries and to invade neighboring interrays where they form ectopic bone. Concomitantly, non-osteoblastic blastema cells and regenerating blood vessels spread into the interrays, resulting in overall disruption of ray-interray organization and irreversible inhibition of fin regeneration. The cyp26a1-expressing niche plays another important role during subsequent regenerative outgrowth, where it facilitates the Shha-promoted proliferation of osteoblasts. Finally, we show that the previously observed distal shift of ray bifurcations in regenerating fins upon RA treatment or amputation close to the bifurcation can be explained by inappropriate preosteoblast alignment and does not necessarily require putative changes in proximodistal information. Our findings uncover a mechanism regulating preosteoblast alignment and maintenance of ray-interray boundaries during fin regeneration.