Mutation in the Ciliary Protein C2CD3 Reveals Organ-Specific Mechanisms of Hedgehog Signal Transduction in Avian Embryos.
Mutation in the Ciliary Protein C2CD3 Reveals Organ-Specific Mechanisms of Hedgehog Signal Transduction in Avian Embryos.
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DOI：
10.3390/jdb9020012
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发表时间：
2021-03-25
影响因子：
2.7
通讯作者：
Brugmann SA
中科院分区：
文献类型：
--
作者：
Brooks EC;Bonatto Paese CL;Carroll AH;Struve JN;Nagy N;Brugmann SA
初级纤毛是普遍存在的基于微管的细胞器，其充当许多发育途径的信号枢纽，最显著的是刺猬（Hh）途径。初级纤毛的结构或功能缺陷导致一类称为纤毛病的疾病。众所周知，初级纤毛参与Hh信号的转导，因此纤毛病经常表现出异常Hh功能的表型。有趣的是，纤毛依赖性Hh信号转导的确切机制尚不清楚，因为一些纤毛病动物模型同时在一个器官系统中存在Hh获得表型，而在另一个器官系统中存在Hh丧失表型。为了更好地了解Hh信号是如何在不同的组织在纤毛病变条件下扰动，我们研究了四个不同的Hh依赖的信号中心，在自然发生的禽纤毛病变突变体talpid2（ta2）。除了众所周知的和以前报道的肢体和颅面畸形，我们观察到背腹图案缺陷的神经管，和缩短的胃肠道。分子分析的元素的Hh途径显示，纤毛的损失影响Hh信号转导的组织特异性的方式在可变水平的途径。这些研究将为受损的纤毛发生如何在组织中差异调节Hh信号提供更多的知识，并将为未来的靶向治疗提供潜在的途径。
Primary cilia are ubiquitous microtubule-based organelles that serve as signaling hubs for numerous developmental pathways, most notably the Hedgehog (Hh) pathway. Defects in the structure or function of primary cilia result in a class of diseases called ciliopathies. It is well known that primary cilia participate in transducing a Hh signal, and as such ciliopathies frequently present with phenotypes indicative of aberrant Hh function. Interestingly, the exact mechanisms of cilia-dependent Hh signaling transduction are unclear as some ciliopathic animal models simultaneously present with gain-of-Hh phenotypes in one organ system and loss-of-Hh phenotypes in another. To better understand how Hh signaling is perturbed across different tissues in ciliopathic conditions, we examined four distinct Hh-dependent signaling centers in the naturally occurring avian ciliopathic mutant talpid2 (ta2). In addition to the well-known and previously reported limb and craniofacial malformations, we observed dorsal-ventral patterning defects in the neural tube, and a shortened gastrointestinal tract. Molecular analyses for elements of the Hh pathway revealed that the loss of cilia impact transduction of an Hh signal in a tissue-specific manner at variable levels of the pathway. These studies will provide increased knowledge into how impaired ciliogenesis differentially regulates Hh signaling across tissues and will provide potential avenues for future targeted therapeutic treatments.
影响因子：
4
作者：
Chang YT;Chaturvedi P;Schock EN;Brugmann SA
通讯作者：
Brugmann SA