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空间多组学揭示了Wnt调制器Dkk2在宫原发育中的作用

Jeremie Oliver Piña^1,2, Resmi Raju¹, Daniela M Roth^1,3

¹Section on Craniofacial Genetic Disorders, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.

bioRxiv : the preprint server for biology

|June 9, 2023

概括

转录因子Pax9对于正常的 palatal 发育至关重要. 它的缺失导致骨质生成受限和口腔裂,由Wnt信号调节器 (如Dkk2) 介导.

科学领域:

头骨面部的发展
分子生物学分子生物学
发育遗传学的发展遗传学.

背景情况:

palatal 裂口是一种常见的遗传性头面部疾病,具有复杂的病因.
了解 palatal osteogenesis 的分子机制对于开发诊断和治疗至关重要.
转录因子Pax9在面发育中起作用,其缺失会导致小鼠的二次口腔裂.

研究的目的:

用Pax9淘汰赛小鼠模型研究Pax9在 palatal骨质生成中的作用.
阐明Pax9与 palatal发育中的骨质分化之间的关系背后的分子机制.

主要方法:

使用了一种Pax9淘汰赛小鼠模型,表现出裂的二次口腔.
采用单核转录组学和染色质可访问性测试.
通过在现场高度复杂的向单细胞空间分析进行验证的发现.

主要成果:

鉴定了Pax9表达细胞和口腔中的骨质性人群之间的明显关系.
已经证明,Pax9的丧失导致空间受限的骨质生成域.
表明Dkk2,一个Wnt路径调节器,限制了这些骨质源域在Pax9缺陷的 palates.

结论:

通过Wnt信号调节器,Pax9通过Wnt信号调节器在 palatal formation 过程中影响骨质生成编程.
对Pax9依赖的Wnt信号的调节失调可能会导致裂口 palatal表型.
这项研究提供了对部发育和裂背后的分子机制的新见解.

关键词:

裂开的 palatus palatus 是一个裂开的 palatus.头骨面部异常头骨面部异常头骨面部生物学/遗传学基因表达基因表达信号传输信号传输单细胞测序单细胞测序

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