Laforest L, Brown C W, Poleo G, Géraudie J, Tada M, Ekker M, Akimenko M A
Loeb Institute for Medical Research, Ottawa Civic Hospital, and Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario, K1Y 4E9, Canada.
Development. 1998 Nov;125(21):4175-84. doi: 10.1242/dev.125.21.4175.
The signaling molecule encoded by Sonic hedgehog (shh) participates in the patterning of several embryonic structures including limbs. During early fin development in zebrafish, a subset of cells in the posterior margin of pectoral fin buds express shh. We have shown that regulation of shh in pectoral fin buds is consistent with a role in mediating the activity of a structure analogous to the zone of polarizing activity (ZPA) (Akimenko and Ekker (1995) Dev. Biol. 170, 243-247). During growth of the bony rays of both paired and unpaired fins, and during fin regeneration, there does not seem to be a region equivalent to the ZPA and one would predict that shh would play a different role, if any, during these processes specific to fish fins. We have examined the expression of shh in the developing fins of 4-week old larvae and in regenerating fins of adults. A subset of cells in the basal layer of the epidermis in close proximity to the newly formed dermal bone structures of the fin rays, the lepidotrichia, express shh, and ptc1 which is thought to encode the receptor of the SHH signal. The expression domain of ptc1 is broader than that of shh and adjacent blastemal cells releasing the dermal bone matrix also express ptc1. Further observations indicate that the bmp2 gene, in addition to being expressed in the same cells of the basal layer of the epidermis as shh, is also expressed in a subset of the ptc1-expressing cells of the blastema. Amputations of caudal fins immediately after the first branching point of the lepidotrichia, and global administration of all-trans-retinoic acid, two procedures known to cause fusion of adjacent rays, result in a transient decrease in the expression of shh, ptc1 and bmp2. The effects of retinoic acid on shh expression occur within minutes after the onset of treatment suggesting direct regulation of shh by retinoic acid. These observations suggest a role for shh, ptc1 and bmp2 in patterning of the dermoskeleton of developing and regenerating teleost fins.
由音猬因子(shh)编码的信号分子参与了包括四肢在内的多个胚胎结构的模式形成。在斑马鱼早期鳍发育过程中,胸鳍芽后缘的一部分细胞表达shh。我们已经表明,胸鳍芽中shh的调控与介导类似于极化活性区(ZPA)的结构的活性作用一致(阿基缅科和埃克(1995年),《发育生物学》170卷,第243 - 247页)。在成对和不成对鳍的骨鳍条生长过程以及鳍再生过程中,似乎不存在与ZPA等效的区域,并且可以预测shh在这些特定于鱼鳍的过程中如果有作用的话,会发挥不同的作用。我们已经研究了shh在4周龄幼虫发育中的鳍以及成年鱼再生鳍中的表达情况。靠近鳍条新形成的真皮骨结构——鳞质鳍条的表皮基底层中的一部分细胞表达shh和ptc1,ptc1被认为是编码SHH信号受体的基因。ptc1的表达域比shh的更宽,并且释放真皮骨基质的相邻胚基细胞也表达ptc1。进一步的观察表明,bmp2基因除了在与shh相同的表皮基底层细胞中表达外,还在胚基中一部分表达ptc1的细胞中表达。在鳞质鳍条第一个分支点之后立即切断尾鳍,以及全身性给予全反式维甲酸,这两种已知会导致相邻鳍条融合的操作,会导致shh、ptc1和bmp2的表达暂时下降。维甲酸对shh表达的影响在治疗开始后几分钟内就会出现,这表明维甲酸对shh有直接调控作用。这些观察结果表明shh、ptc1和bmp2在硬骨鱼发育和再生鳍的真皮骨骼模式形成中发挥作用。