Hedgehog (Hh)蛋白家族调控细胞生长，细胞存活，细胞命运决定等脊椎动物几乎所有模式形成过程的各个方面。单独的一种形态发生子(morphogen)能产生这么广泛的影响是可能的，因为细胞对Hedgehog信号通路的响应依赖于不同细胞种类、接收到的Hedgehog信号剂量强度、以及相应Hedgehog信号的具体时间。

并且Hedgehog的信号梯度由加工、分泌、运输Hedgehog信号所需蛋白特化。细胞响应机制又协同负反馈循环进一步微调Hedgehog信号。影响到Hedgehog信号转导途径的生殖细胞突变体往往伴随发育过程紊乱，同时，激活Hedgehog信号转导通路的体细胞突变往往伴随多种人类癌症的发生。

这篇综述详细介绍了最新Hedgehog信号转导途径研究进展，阐述了Hedgehog信号转导通路的发生机制及发育生物学功能。另外，本综述也讨论了人类疾病发生的病理生物学过程，以探寻人类疾病的潜在治疗方法。

http://www.dreamfreeblog.com/hedgehog-functions-and-mechanisms-316.html

GENES & DEVELOPMENT 22:2454-2472, 2008
©2008 by Cold Spring Harbor Laboratory Press; ISSN 0890-9369/ $5.00
OPEN ACCESS ARTICLE
This Article
OPEN ACCESS ARTICLE

REVIEW

Hedgehog: functions and mechanisms
Markku Varjosalo and Jussi Taipale1

Department of Molecular Medicine, National Public Health Institute (KTL), and Genome-Scale Biology Program, Biomedicum Helsinki, Institute of Biomedicine and High Throughput Center, Faculty of Medicine, University of Helsinki, Helsinki FI-00014, Finland

The Hedgehog (Hh) family of proteins control cell growth, survival, and fate, and pattern almost every aspect of the vertebrate body plan. The use of a single morphogen for such a wide variety of functions is possible because cellular responses to Hh depend on the type of responding cell, the dose of Hh received, and the time cells are exposed to Hh. The Hh gradient is shaped by several proteins that are specifically required for Hh processing, secretion, and transport through tissues. The mechanism of cellular response, in turn, incorporates multiple feedback loops that fine-tune the level of signal sensed by the responding cells. Germline mutations that subtly affect Hh pathway activity are associated with developmental disorders, whereas somatic mutations activating the pathway have been linked to multiple forms of human cancer. This review focuses broadly on our current understanding of Hh signaling, from mechanisms of action to cellular and developmental functions. In addition, we review the role of Hh in the pathogenesis of human disease and the possibilities for therapeutic intervention.

[Keywords: hedgehog; signal transduction; cancer; development; transcription]

1 Corresponding author.

http://genesdev.cshlp.org/cgi/content/abstract/22/18/2454

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