Induction and prepatterning of the zebrafish pectoral fin bud requires axial retinoic acid signaling
Induction and prepatterning of the zebrafish pectoral fin bud requires axial retinoic acid signaling
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DOI：
10.1242/dev.02438
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发表时间：
2006-07-15
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：
Gibert, Yann;Gajewski, Alexandra;Begemann, Gerrit
脊椎动物的前肢从侧板中胚层（LPM）的两侧附属物出现。aldh 1a 2（raldh 2），一个胚胎表达的基因编码的维甲酸（RA）合成酶的突变体，已被用来表明，肢体发育和图案的肢芽是至关重要的依赖于RA信号。然而，RA信号在这些过程中的时间和细胞起源仍然没有得到很好的解决。我们已经使用遗传学和RA信号的化学调节剂来解决斑马鱼中的这些问题。通过拯救胸鳍诱导的aldh 1a 2/neckless突变体与外源RA和通过阻断RA信号在野生型胚胎，我们发现，RA作为一个许可的信号，需要在六至八体节阶段胸鳍诱导。细胞移植实验表明，RA生产不仅是至关重要的侧翼体节所需的，但足以允许鳍芽启动时，树干中胚层基因消融。在后者的条件下，中间中胚层单独不能诱导胸鳍领域的LPM。我们进一步表明，诱导的鳍领域是直接遵循的体节衍生的RA信号建立一个prepattern的前后命运的冷凝鳍间充质的持续需求。这一过程是由转录因子hand 2的持续表达介导的，通过该转录因子hand 2，鳍场被连续地后向化，并且在肢芽形成之前持续长达几个小时。因此，RA信号从侧翼体节起着双重早期作用的冷凝肢芽间充质。
Vertebrate forelimbs arise as bilateral appendages from the lateral plate mesoderm (LPM). Mutants in aldh1a2 (raldh2), an embryonically expressed gene encoding a retinoic acid (RA)-synthesizing enzyme, have been used to show that limb development and patterning of the limb bud are crucially dependent on RA signaling. However, the timing and cellular origin of RA signaling in these processes have remained poorly resolved. We have used genetics and chemical modulators of RA signaling to resolve these issues in the zebrafish. By rescuing pectoral fin induction in the aldh1a2/neckless mutant with exogenous RA and by blocking RA signaling in wild-type embryos, we find that RA acts as a permissive signal that is required during the six- to eight-somite stages for pectoral fin induction. Cell-transplantation experiments show that RA production is not only crucially required from flanking somites, but is sufficient to permit fin bud initiation when the trunk mesoderm is genetically ablated. Under the latter condition, intermediate mesoderm alone cannot induce the pectoral fin field in the LPM. We further show that induction of the fin field is directly followed by a continued requirement for somite-derived RA signaling to establish a prepattern of anteroposterior fates in the condensing fin mesenchyme. This process is mediated by the maintained expression of the transcription factor hand2, through which the fin field is continuously posteriorized, and lasts up to several hours prior to limb-budding. Thus, RA signaling from flanking somites plays a dual early role in the condensing limb bud mesenchyme.