Interspecies transcriptomics identify genes that underlie disproportionate foot growth in jerboas.
Interspecies transcriptomics identify genes that underlie disproportionate foot growth in jerboas.
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DOI：
10.1016/j.cub.2021.10.063
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发表时间：
2022-01-24
期刊：
影响因子：
--
通讯作者：
Cooper KL
中科院分区：
文献类型：
--
作者：
Saxena A;Sharma V;Muthuirulan P;Neufeld SJ;Tran MP;Gutierrez HL;Chen KD;Erberich JM;Birmingham A;Capellini TD;Cobb J;Hiller M;Cooper KL
尽管脊椎动物肢体比例的多样性和我们对驱动骨骼伸长的遗传机制的深刻理解，但对任何物种中个体骨骼如何达到不同长度知之甚少。在这里，我们直接比较了小鼠（小家鼠）和两足跳鼠（Jaculus jaculus）的同源生长软骨的转录组，后者具有“小鼠样”的手臂，但脚的跖骨非常长。两个物种的跖骨和前臂的交叉基因表达差异显示，约10%的orthopathic基因与新生跳鼠脚的不成比例的快速伸长有关。这些包括基因和丰富的途径，以前没有相关的endochondrialelongation，以及那些可能多样化的骨骼比例，除了他们已知的要求，骨生长在整个骨骼。我们还确定了转录调节因子，可能作为“节点”的物种之间的基因组表达的全面差异。其中，近端肢体伸长所必需的Shox 2已在跳鼠的跖骨中表达，而在其他脊椎动物中尚未检测到。我们表明，Shox2是足以增加小鼠远端肢体长度，附近的推定顺式调节区是优先访问跳鼠跖骨。除了可能直接促进生长的机制外，我们还发现了跳鼠足伸长可能部分通过去抑制潜在生长潜力而发生的证据。我们在这里确定的基因和途径提供了一个框架，以了解骨骼生长的模块化遗传控制和脊椎动物肢体比例的显着可塑性。跳鼠的长脚是怎么来的？Saxena等人使用种间转录组方法鉴定了与跳鼠跖骨与小鼠相比不成比例伸长相关的基因。总而言之，他们提供了一个框架，以了解骨骼生长的模块化遗传控制和肢体比例的显着可塑性。
Despite the great diversity of vertebrate limb proportion and our deep understanding of the genetic mechanisms that drive skeletal elongation, little is known about how individual bones reach different lengths in any species. Here, we directly compare the transcriptomes of homologous growth cartilages of the mouse (Mus musculus) and bipedal jerboa (Jaculus jaculus), the latter of which has ‘mouse-like’ arms but extremely long metatarsals of the feet. Intersecting gene expression differences in metatarsals and forearms of the two species revealed that about 10% of orthologous genes are associated with the disproportionately rapid elongation of neonatal jerboa feet. These include genes and enriched pathways not previously associated with endochondral elongation as well as those that might diversify skeletal proportion in addition to their known requirements for bone growth throughout the skeleton. We also identified transcription regulators that might act as ‘nodes’ for sweeping differences in genome expression between species. Among these, Shox2, which is necessary for proximal limb elongation, has gained expression in jerboa metatarsals where it has not been detected in other vertebrates. We show that Shox2 is sufficient to increase mouse distal limb length, and a nearby putative cis-regulatory region is preferentially accessible in jerboa metatarsals. In addition to mechanisms that might directly promote growth, we found evidence that jerboa foot elongation may occur in part by de-repressing latent growth potential. The genes and pathways that we identified here provide a framework to understand the modular genetic control of skeletal growth and the remarkable malleability of vertebrate limb proportion. How did the jerboa get its long feet? Using an interspecies transcriptome approach, Saxena et al. identify genes associated with the disproportionate elongation of jerboa metatarsals compared to mouse. Altogether, they provide a framework to understand the modular genetic control of skeletal growth and the striking malleability of limb proportion.
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