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Hh 形态发生素源移动对信号转导动力学的影响。

The effects of Hh morphogen source movement on signaling dynamics.

机构信息

Departmento de Física de la Materia Condensada, Instituto de Física de la Materia Condensada (IFIMAC), Facultad de Ciencias, and Centro de Biología Molecular Severo Ochoa (CBMSO, CSIC-UAM), Universidad Autónoma de Madrid, 28049 Madrid, Spain.

Gene Expression and Morphogenesis Department, CABD (Andalusian Centre for Developmental Biology), CSIC/Universidad Pablo de Olavide/Junta de Andalucia, Campus UPO, 41013 Seville, Spain.

出版信息

Development. 2022 Dec 1;149(23). doi: 10.1242/dev.199842. Epub 2022 Dec 7.

DOI:10.1242/dev.199842
PMID:36355083
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10114110/
Abstract

Morphogens of the Hh family trigger gene expression changes in receiving cells in a concentration-dependent manner to regulate their identity, proliferation, death or metabolism, depending on the tissue or organ. This variety of responses relies on a conserved signaling pathway. Its logic includes a negative-feedback loop involving the Hh receptor Ptc. Here, using experiments and computational models we study and compare the different spatial signaling profiles downstream of Hh in several developing Drosophila organs. We show that the spatial distributions of Ptc and the activator transcription factor CiA in wing, antenna and ocellus show similar features, but are markedly different from that in the compound eye. We propose that these two profile types represent two time points along the signaling dynamics, and that the interplay between the spatial displacement of the Hh source in the compound eye and the negative-feedback loop maintains the receiving cells effectively in an earlier stage of signaling. These results show how the interaction between spatial and temporal dynamics of signaling and differentiation processes may contribute to the informational versatility of the conserved Hh signaling pathway.

摘要

Hh 家族的形态发生素以浓度依赖的方式触发受体细胞中的基因表达变化,从而根据组织或器官调节其身份、增殖、死亡或代谢。这种多样化的反应依赖于保守的信号通路。其逻辑包括涉及 Hh 受体 Ptc 的负反馈环。在这里,我们使用实验和计算模型研究并比较了 Hh 在几种发育中的果蝇器官中信号的不同空间分布特征。我们表明,翅膀、触角和小眼的 Ptc 和激活转录因子 CiA 的空间分布具有相似的特征,但与复眼明显不同。我们提出,这两种类型的分布代表了信号动力学的两个时间点,而在复眼中 Hh 源的空间位移与负反馈环之间的相互作用使感受细胞有效地保持在信号的早期阶段。这些结果表明,信号和分化过程的空间和时间动态之间的相互作用如何有助于保守的 Hh 信号通路的信息多功能性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a875/10114110/7a5cda008f71/develop-149-199842-g4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a875/10114110/d512b674db31/develop-149-199842-g1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a875/10114110/b67dda8924e2/develop-149-199842-g2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a875/10114110/451eb2f749a3/develop-149-199842-g3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a875/10114110/7a5cda008f71/develop-149-199842-g4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a875/10114110/d512b674db31/develop-149-199842-g1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a875/10114110/b67dda8924e2/develop-149-199842-g2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a875/10114110/451eb2f749a3/develop-149-199842-g3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a875/10114110/7a5cda008f71/develop-149-199842-g4.jpg

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2
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Dynamic Hh signalling can generate temporal information during tissue patterning.动态 HH 信号可以在组织模式形成过程中产生时间信息。
Development. 2019 Apr 25;146(8):dev176933. doi: 10.1242/dev.176933.
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Morphogen gradient reconstitution reveals Hedgehog pathway design principles.形态发生梯度重建揭示 Hedgehog 信号通路设计原则。
Science. 2018 May 4;360(6388):543-548. doi: 10.1126/science.aao0645. Epub 2018 Apr 5.
5
Essential basal cytonemes take up Hedgehog in the wing imaginal disc.必需的基底细胞丝在翅成虫盘摄取刺猬蛋白。
Development. 2017 Sep 1;144(17):3134-3144. doi: 10.1242/dev.149856. Epub 2017 Jul 25.
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