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Development and patterning of rib primordia are dependent on associated musculature.
Developmental Biology ( IF 2.7 ) Pub Date : 2020-08-05 , DOI: 10.1016/j.ydbio.2020.07.015
William M Wood 1 , Chelsea Otis 1 , Shervin Etemad 1 , David J Goldhamer 1
Affiliation  

The importance of skeletal muscle for rib development and patterning in the mouse embryo has not been resolved, largely because different experimental approaches have yielded disparate results. In this study, we utilize both gene knockouts and muscle cell ablation approaches to re-visit the extent to which rib growth and patterning are dependent on developing musculature. Consistent with previous studies, we show that rib formation is highly dependent on the MYOD family of myogenic regulatory factors (MRFs), and demonstrate that the extent of rib formation is gene-, allele-, and dosage-dependent. In the absence of Myf5 and MyoD, one allele of Mrf4 is sufficient for extensive rib growth, although patterning is abnormal. Under conditions of limiting MRF dosage, MyoD is identified as a positive regulator of rib patterning, presumably due to improved intercostal muscle development. In contrast to previous muscle ablation studies, we show that diphtheria toxin A (DTA)-mediated ablation of muscle progenitors or differentiated muscle, using MyoDiCre or HSA-Cre drivers, respectively, profoundly disrupts rib growth and patterning. Further, a comparison of three independently derived Rosa26-based DTA knockin alleles demonstrates that the degree of rib perturbations in MyoDiCre/DTA embryos is markedly dependent on the DTA allele used, and may in part explain discrepancies with previous findings. The results support the conclusion that the extent and quality of rib formation is largely dependent on the dosage of Myf5 and Mrf4, and that both early myotome-sclerotome interactions, as well as later muscle-rib interactions, are important for proper rib growth and patterning.



中文翻译:

肋骨原基的发育和模式取决于相关的肌肉组织。

骨骼肌对小鼠胚胎肋骨发育和图案形成的重要性尚未得到解决,主要是因为不同的实验方法产生了不同的结果。在这项研究中,我们利用基因敲除和肌肉细胞消融方法重新审视肋骨生长和图案形成依赖于肌肉组织发育的程度。与之前的研究一致,我们表明肋骨形成高度依赖于肌源性调节因子 (MRF) 的 MYOD 家族,并证明肋骨形成的程度是基因、等位基因和剂量依赖性的。在没有Myf5MyoD的情况下,Mrf4 的一个等位基因尽管图案不正常,但足以进行广泛的肋骨生长。在限制 MRF 剂量的条件下,MyoD被确定为肋骨图案的正调节器,可能是由于肋间肌肉发育的改善。与之前的肌肉消融研究相比,我们发现白喉毒素 A (DTA) 介导的肌肉祖细胞或分化肌肉消融,分别使用MyoD iCre或 HSA-Cre 驱动程序,深刻地破坏了肋骨的生长和图案。此外,三个独立衍生的基于Rosa26的 DTA 敲入等位基因的比较表明,MyoD iCre中肋骨扰动的程度/DTA 胚胎明显依赖于所使用的 DTA 等位基因,并且可能部分解释了与先前发现的差异。结果支持以下结论,即肋骨形成的程度和质量在很大程度上取决于Myf5Mrf4的剂量,并且早期的肌节-巩膜相互作用以及后期的肌肉-肋骨相互作用对于适当的肋骨生长和图案形成都很重要.

更新日期:2020-08-05
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