Retinoic acid-independent expression of Meis2 during autopod patterning in the developing bat and mouse limb.
Retinoic acid-independent expression of Meis2 during autopod patterning in the developing bat and mouse limb.
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DOI：
10.1186/s13227-015-0001-y
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发表时间：
2015
期刊：
影响因子：
4.1
通讯作者：
Illing N
中科院分区：
文献类型：
--
作者：
Mason MK;Hockman D;Curry L;Cunningham TJ;Duester G;Logan M;Jacobs DS;Illing N
由于空中和陆地运动的不同要求，蝙蝠的前肢（支撑翼膜的长手指）和后肢（短，通常是自由的手指）明显不同。在胚胎发育过程中，蝙蝠前肢的形态与小鼠和小鸡的前肢形态明显不同，这为识别在肢体模式中发挥重要作用的基因提供了另一种范例。通过对发育中的纳塔尔长指蝙蝠（Miniopterus natalensis）前肢和后肢的转录组分析，我们证明转录因子 Meis2 在蝙蝠前肢自足中的表达量显着高于后肢。通过逆转录酶和定量聚合酶链反应 (RT-qPCR) 以及整体原位杂交进行的验证表明，传统上称为早期近端肢芽标记的 Meis2 在来自 CS16 的蝙蝠前肢自足中表达上调。 Meis2 表达定位于扩张的指间网带以及连接机翼与后肢和尾部的膜。在小鼠中，Meis2 也在组织退化之前的指间区域表达。这种指间 Meis2 表达不会被视黄酸 (RA) 信号激活，因为它存在于缺乏 RA 的 Rdh10trex/trex 小鼠保留的指间组织中。此外，编码 RA 合成酶 Rdh10 和 Aldh1a2 以及 RA 核受体 Rarβ 的基因在蝙蝠前肢和后肢指间组织中强烈表达，表明蝙蝠中保留指间组织的机制也独立于 RA 信号传导而发生。哺乳动物指间 Meis2 表达以及蝙蝠翅膀指间蹼中的上调表明 Meis2 在自足发育中发挥重要作用。指间 Meis2 表达与 RA 无关，并且蝙蝠翅膀中指间蹼的保留不是由于抑制 RA 诱导的细胞死亡。相反，RA信号传导可能在蝙蝠前肢指间组织变薄（而不是完全丧失）中发挥作用，而Meis2可能在蝙蝠和小鼠自足发育过程中与其他因素相互作用，以维持有助于数字模式和生长的指间细胞池。本文的在线版本 (doi:10.1186/s13227-015-0001-y) 包含补充材料，可供授权用户使用。
The bat has strikingly divergent forelimbs (long digits supporting wing membranes) and hindlimbs (short, typically free digits) due to the distinct requirements of both aerial and terrestrial locomotion. During embryonic development, the morphology of the bat forelimb deviates dramatically from the mouse and chick, offering an alternative paradigm for identifying genes that play an important role in limb patterning. Using transcriptome analysis of developing Natal long-fingered bat (Miniopterus natalensis) fore- and hindlimbs, we demonstrate that the transcription factor Meis2 has a significantly higher expression in bat forelimb autopods compared to hindlimbs. Validation by reverse transcriptase and quantitative polymerase chain reaction (RT-qPCR) and whole mount in situ hybridisation shows that Meis2, conventionally known as a marker of the early proximal limb bud, is upregulated in the bat forelimb autopod from CS16. Meis2 expression is localised to the expanding interdigital webbing and the membranes linking the wing to the hindlimb and tail. In mice, Meis2 is also expressed in the interdigital region prior to tissue regression. This interdigital Meis2 expression is not activated by retinoic acid (RA) signalling as it is present in the retained interdigital tissue of Rdh10trex/trex mice, which lack RA. Additionally, genes encoding RA-synthesising enzymes, Rdh10 and Aldh1a2, and the RA nuclear receptor Rarβ are robustly expressed in bat fore- and hindlimb interdigital tissues indicating that the mechanism that retains interdigital tissue in bats also occurs independently of RA signalling. Mammalian interdigital Meis2 expression, and upregulation in the interdigital webbing of bat wings, suggests an important role for Meis2 in autopod development. Interdigital Meis2 expression is RA-independent, and retention of interdigital webbing in bat wings is not due to the suppression of RA-induced cell death. Rather, RA signalling may play a role in the thinning (rather than complete loss) of the interdigital tissue in the bat forelimb, while Meis2 may interact with other factors during both bat and mouse autopod development to maintain a pool of interdigital cells that contribute to digit patterning and growth. The online version of this article (doi:10.1186/s13227-015-0001-y) contains supplementary material, which is available to authorized users.