视黄酸分解是两栖动物肢体再生过程中近端位置特征的必要条件

bioRxiv Pub Date : 2024-08-09 DOI:10.1101/2024.08.07.607055
Timothy J. Duerr, Melissa Miller, Sage Kumar, Dareen Bakr, Jackson R. Griffiths, Aditya K. Gautham, Danielle Douglas, S. R. Voss, James R. Monaghan
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引用次数: 0

摘要

肢体截肢后,再生肢体会保留其近端(PD)位置特征。这种位置特征由PD模式基因遗传编码,这些基因指示胚泡细胞再生适当的PD肢段。已知视黄酸(RA)可指定肢体近端特征,但视黄酸信号水平如何在胚泡中建立尚不清楚。在这里,我们发现通过 CYP26B1 分解 RA 对确定胚泡内的 RA 信号水平至关重要。抑制 CYP26B1 可在分子上将远端胚泡重新编程为更近端特征,从而表征了过量 RA 的影响。我们发现 Shox 是一种 RA 响应基因,它在近端和远端截肢肢体中表达不同。消减 Shox 会导致肢体缩短,其近端骨骼元素无法启动软骨内骨化。这些结果表明,在肢体再生过程中,PD的位置特性是由RA降解和RA反应基因决定的,而RA反应基因可调控PD骨骼元件的形成。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Retinoic acid breakdown is required for proximodistal positional identity during amphibian limb regeneration
Regenerating limbs retain their proximodistal (PD) positional identity following amputation. This positional identity is genetically encoded by PD patterning genes that instruct blastema cells to regenerate the appropriate PD limb segment. Retinoic acid (RA) is known to specify proximal limb identity, but how RA signaling levels are established in the blastema is unknown. Here, we show that RA breakdown via CYP26B1 is essential for determining RA signaling levels within blastemas. CYP26B1 inhibition molecularly reprograms distal blastemas into a more proximal identity, phenocopying the effects of administering excess RA. We identify Shox as an RA-responsive gene that is differentially expressed between proximally and distally amputated limbs. Ablation of Shox results in shortened limbs with proximal skeletal elements that fail to initiate endochondral ossification. These results suggest that PD positional identity is determined by RA degradation and RA-responsive genes that regulate PD skeletal element formation during limb regeneration.
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