Development and patterning of rib primordia are dependent on associated musculature.
Development and patterning of rib primordia are dependent on associated musculature.
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DOI：
10.1016/j.ydbio.2020.07.015
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发表时间：
2020-12-01
影响因子：
2.7
通讯作者：
Goldhamer DJ
中科院分区：
文献类型：
--
作者：
Wood WM;Otis C;Etemad S;Goldhamer DJ
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的方法来重新访问肋骨生长和图案的程度依赖于发育中的肌肉组织。与以前的研究一致，我们发现肋骨形成高度依赖于MYOD家族的生肌调节因子（MRF），并证明肋骨形成的程度是基因，等位基因和剂量依赖性的。在缺乏Myf 5和MyoD的情况下，Mrf 4的一个等位基因足以进行广泛的肋骨生长，尽管图案是异常的。在限制MRF剂量的条件下，MyoD被鉴定为肋骨图案形成的正调节剂，推测是由于改善了肋间肌肉发育。与以前的肌肉消融研究相反，我们表明，白喉毒素A（DTA）介导的肌肉祖细胞或分化的肌肉消融，分别使用MyoDiCre或HSA-Cre驱动程序，深刻地破坏肋骨生长和图案。此外，三个独立衍生的Rosa 26为基础的DTA敲入等位基因的比较表明，在MyoDiCre/DTA胚胎肋骨扰动的程度是显着依赖于所使用的DTA等位基因，并可能在一定程度上解释与以前的研究结果的差异。结果支持了以下结论：肋骨形成的程度和质量在很大程度上取决于Myf 5和Mrf 4的剂量，并且早期肌节-硬节相互作用以及后期肌肉-肋骨相互作用对于肋骨的正常生长和形成模式都很重要。
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.
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影响因子：
2.4
作者：
Berti F;Nogueira JM;Wöhrle S;Sobreira DR;Hawrot K;Dietrich S
通讯作者：
Dietrich S
影响因子：
10.5
作者：
Akiyama, H;Chaboissier, MC;de Crombrugghe, B
通讯作者：
de Crombrugghe, B
影响因子：
4.6
作者：
Hinits, Yaniv;Osborn, Daniel P. S.;Hughes, Simon M.
通讯作者：
Hughes, Simon M.
影响因子：
4.6
作者：
Gensch, Nicole;Borchardt, Thilo;Braun, Thomas
通讯作者：
Braun, Thomas
影响因子：
1.2
作者：
Hinits, Yaniv;Osborn, Daniel P. S.;Carvajal, Jaime J.;Rigby, Peter W. J.;Hughes, Simon M.
通讯作者：
Hughes, Simon M.