包括 Zfhx4 在内的基因在小鼠和斑马鱼中的表达分析揭示了颅面发育的时间空间保守分子基础。

IF 2 3区 生物学 Q2 ANATOMY & MORPHOLOGY Developmental Dynamics Pub Date : 2024-09-25 DOI:10.1002/dvdy.740
Shujie Liu, Lin Xu, Makoto Kashima, Rika Narumi, Yoshifumi Takahata, Eriko Nakamura, Hirotoshi Shibuya, Masaru Tamura, Yuki Shida, Toshihiro Inubushi, Yuko Nukada, Masaaki Miyazawa, Kenji Hata, Riko Nishimura, Takashi Yamashiro, Junichi Tasaki, Hiroshi Kurosaka
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引用次数: 0

摘要

背景:胚胎颅面发育涉及脊椎动物间进化保守的若干细胞和分子事件。小鼠和斑马鱼等脊椎动物模型已被用于研究人类颅面疾病(包括口面裂)的分子和细胞病因。然而,这两个物种胚胎发育的分子机制尚不清楚。因此,阐明疾病模型之间颅面发育的共同机制对于理解各个物种表型的内在机制至关重要:结果:我们选择小鼠和斑马鱼作为模型生物,比较胚胎颅面发育过程中的各种事件。通过全面和阶段匹配的基因表达分析,我们确定了这些物种之间具有相似时间表达模式的基因(Sox9、Zfhx3 和 4、Cjun 和 Six1)。表达分析表明,在假定的相应组织(如小鼠腭和斑马鱼蝶骨板)中也有类似的基因表达。此外,Zfhx4/zfhx4 是人类颅面畸形(包括口面裂)的致病基因,对这两个物种的 Zfhx4/zfhx4 功能缺失分析分别导致小鼠和斑马鱼的腭和乙状板等骨骼元素畸形:这些结果表明,这些疾病模型具有共同的分子机制,突出了它们在模拟人类颅面缺陷方面的实用性。
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Expression analysis of genes including Zfhx4 in mice and zebrafish reveals a temporospatial conserved molecular basis underlying craniofacial development.

Background: Embryonic craniofacial development involves several cellular and molecular events that are evolutionarily conserved among vertebrates. Vertebrate models such as mice and zebrafish have been used to investigate the molecular and cellular etiologies underlying human craniofacial disorders, including orofacial clefts. However, the molecular mechanisms underlying embryonic development in these two species are unknown. Therefore, elucidating the shared mechanisms of craniofacial development between disease models is crucial to understanding the underlying mechanisms of phenotypes in individual species.

Results: We selected mice and zebrafish as model organisms to compare various events during embryonic craniofacial development. We identified genes (Sox9, Zfhx3 and 4, Cjun, and Six1) exhibiting similar temporal expression patterns between these species through comprehensive and stage-matched gene expression analyses. Expression analysis revealed similar gene expression in hypothetically corresponding tissues, such as the mice palate and zebrafish ethmoid plate. Furthermore, loss-of-function analysis of Zfhx4/zfhx4, a causative gene of human craniofacial anomalies including orofacial cleft, in both species resulted in deformed skeletal elements such as the palatine and ethmoid plate in mice and zebrafish, respectively.

Conclusions: These results demonstrate that these disease models share common molecular mechanisms, highlighting their usefulness in modeling craniofacial defects in humans.

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来源期刊
Developmental Dynamics
Developmental Dynamics 生物-发育生物学
CiteScore
5.10
自引率
8.00%
发文量
116
审稿时长
3-8 weeks
期刊介绍: Developmental Dynamics, is an official publication of the American Association for Anatomy. This peer reviewed journal provides an international forum for publishing novel discoveries, using any model system, that advances our understanding of development, morphology, form and function, evolution, disease, stem cells, repair and regeneration.
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