Review
Cell Biology
Sara Douceau, Tanya Deutsch Guerrero, Julien Ferent
Summary: A morphogen is a signaling molecule that induces cellular responses depending on its concentration. Sonic Hedgehog (Shh) is an important morphogen involved in various processes during embryonic development. This review discusses the sources of Shh during nervous system development, mechanisms of its distribution in surrounding tissues, and the consequences of disrupted distribution on neurodevelopmental disorders and cancers. Additionally, it highlights the use of contemporary techniques, like organoids, in re-examining the classical gradient model.
Article
Multidisciplinary Sciences
Shyam K. Akula, Jack H. Marciano, Youngshin Lim, David Exposito-Alonso, Norma K. Hylton, Grace H. Hwang, Jennifer E. Neil, Nicole Dominado, Rosie K. Bunton-Stasyshyn, Janet H. T. Song, Maya Talukdar, Aloisia Schmid, Lydia Teboul, Alisa Mo, Taehwan Shin, Benjamin Finander, Samantha G. Beck, Rebecca C. Yeh, Aoi Otani, Xuyu Qian, Ellen M. DeGennaro, Fowzan S. Alkuraya, Sateesh Maddirevula, Gregory D. Cascino, Caterina Giannini, Lindsay C. Undiagnosed Diseases Network, Lindsay C. Burrage, Jill A. Rosenfield, Shamika Ketkar, Gary D. Clark, Carlos Bacino, Richard A. Lewis, Rosalind A. Segal, J. Fernando Bazan, Kelly A. Smith, Jeffrey A. Golden, Ginam Cho, Christopher A. Walsh
Summary: This study reveals the role of TMEM161B in regulating Sonic hedgehog signaling and cerebral cortical gyration during embryonic development. Mutations in TMEM161B are associated with multiple abnormalities including polymicrogyria. TMEM161B is involved in primary ciliary structure and its dysfunction may contribute to ciliary-related phenotypes.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biology
Rachana Deven Somaiya, Katelyn Stebbins, Ellen C. Gingrich, Hehuang Xie, John N. Campbell, A. Denise R. Garcia, Michael A. Fox
Summary: Axons of retinal ganglion cells induce astrocytes in the visual thalamus to generate Fgf15, which influences the migration of interneurons. The release of SHH from retinal axons is crucial for the recruitment of interneurons.
Article
Biophysics
Vijay Velagala, Jeremiah J. Zartman
Summary: Epithelial folding in Drosophila embryos occurs through local apical constriction and tissue-level compressive forces. The process is also accompanied by spatiotemporal pulses of Hedgehog signaling.
BIOPHYSICAL JOURNAL
(2021)
Article
Surgery
Ronan J. Kelly, Amir M. Ansari, Tomoharu Miyashita, Marianna Zahurak, Frank Lay, A. Karim Ahmed, Louis J. Born, Maryam K. Pezhouh, Kevan J. Salimian, Christopher Ng, Aerielle E. Matsangos, Anne-Heloise Stricker-Krongrad, Ken-ichi Mukaisho, Guy P. Marti, Christine H. Chung, Marcia I. Canto, Michelle A. Rudek, Stephen J. Meltzer, John W. Harmon
Summary: Itraconazole significantly reduces the development of esophageal adenocarcinoma and SHH expression in a preclinical animal model of Barrett's Metaplasia. In humans, BE tissue expresses higher levels of SHH, Indian Hedgehog, and bone morphogenic protein compared to normal squamous esophageal epithelium.
Review
Biochemistry & Molecular Biology
Marilyn D. Resh
Summary: This review discusses the role of Hedgehog acyltransferase (Hhat) in Hedgehog signaling, the importance of palmitoylation, and the potential involvement of Hhat in various cancers. Targeting hedgehog palmitoylation by inhibiting Hhat is considered a promising intervention in human disease.
Article
Multidisciplinary Sciences
Naoko Koyano-Nakagawa, Wuming Gong, Satyabrata Das, Joshua W. M. Theisen, Tran B. Swanholm, Daniel Van Ly, Nikita Dsouza, Bhairab N. Singh, Hiroko Kawakami, Samantha Young, Katherine Q. Chen, Yasuhiko Kawakami, Daniel J. Garry
Summary: ETV2 acts as a pioneer transcription factor in initiating Shh expression by modifying the chromatin status of the ZRS enhancer. It plays a crucial role in nucleosomal displacement and transcriptional activation, regulating the onset of Shh expression in limb buds.
NATURE COMMUNICATIONS
(2022)
Article
Cell Biology
Dominique Manikowski, Philipp Kastl, Sabine Schuermann, Kristina Ehring, Georg Steffes, Petra Jakobs, Kay Grobe
Summary: The study reveals that C-terminal cholesteroylation of Hedgehog is essential for early steps of production and maturation, but dispensable for signal reception at receiving cells.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Biology
Koh Onimaru, Kaori Tatsumi, Chiharu Tanegashima, Mitsutaka Kadota, Osamu Nishimura, Shigehiro Kuraku
Summary: This study investigates genetic apparatuses distinguishing fish fins from tetrapod limbs, revealing mass heterochrony and conservation of gene expression. Open-chromatin analysis suggests transiently increased access to conserved regulatory sequences during mid-stage limb development. Early and late stages of fin/limb development are more permissive to mutations, while middle stages are constrained by regulatory complexity.
Article
Cell Biology
Juliana Gusson Roscito, Katrin Sameith, Bogdan Mikhailovich Kirilenko, Nikolai Hecker, Sylke Winkler, Andreas Dahl, Miguel Trefaut Rodrigues, Michael Hiller
Summary: A comparative genomic analysis of limbless reptiles reveals that shared divergence occurs more often at the level of signaling pathways and patterning mechanisms, rather than in individual limb regulatory elements. Different mechanisms, such as different regulatory elements associated with the same limb genes and/or patterning mechanisms, may contribute to limb loss in reptiles.
Article
Cell Biology
Sruthi Purushothaman, Brianda B. Lopez Avina, Ashley W. Seifert
Summary: This study demonstrates the role of Sonic hedgehog (Shh) signaling in the development of the forelimb in axolotls, showing that Shh is not only involved in limb patterning, but also directs the expansion and survival of limb progenitor cells. The study suggests that urodeles have evolved a unique mode of limb development compared to other tetrapods.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Yitian Luo, Guoyue Wan, Xiang Zhang, Xuan Zhou, Qiuwen Wang, Jialin Fan, Hongmin Cai, Liya Ma, Hailong Wu, Qianhui Qu, Yao Cong, Yun Zhao, Dianfan Li
Summary: The study reconstituted Patched (Ptc1) into lipid nanodiscs and found that Ptc1 can form dimers under different membrane curvatures, providing a plausible framework for Ptc1 clustering in highly curved caveolae.
Article
Multidisciplinary Sciences
Irene Delgado, Giovanna Giovinazzo, Susana Temino, Yves Gauthier, Aurelio Balsalobre, Jacques Drouin, Miguel Torres
Summary: Meis1 and Meis2 are homeodomain transcription factors that regulate organogenesis by cooperating with Hox proteins. Inactivation of Meis1/2 in the lateral plate mesoderm leads to limb agenesis in mouse embryos, with Meis and Tbx factors co-binding and co-regulating enhancers of Fgf10. Limbs with deleted Meis alleles show skeletal hypoplasia and agenesis of posterior elements due to their early role in establishing limb antero-posterior prepattern.
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Sangwoo Shim, Raman Goyal, Alexios A. Panoutsopoulos, Olga A. Balashova, David Lee, Laura N. Borodinsky
Summary: The balance between neural stem cell proliferation and neuronal differentiation is crucial for the development of the nervous system. We found that Sonic hedgehog (Shh) enhances Ca2+ activity at the cilia of developing Xenopus laevis embryos, which promotes neuronal differentiation and inhibits proliferative signaling. These findings provide potential targets for the treatment of brain tumors and neurodevelopmental disorders.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Neurosciences
Fengjiao Liu, Jingyuan Shao, Haihong Yang, Guochao Yang, Qian Zhu, Yan Wu, Lingling Zhu, Haitao Wu
Summary: Our study found that Rack1 was significantly upregulated in the majority of human cerebellar MB tumors. Genetic ablation of Rack1 expression in SHH-MB tumor mice could significantly inhibit MB proliferation, reduce the tumor size, and prolong the survival of tumor rescue mice. Further studies showed that in rescue mice, while apoptosis and autophagy levels were unaffected, the expression of Gli1 and HDAC2 was significantly decreased suggesting the inactivation of the SHH signaling pathway.
CNS NEUROSCIENCE & THERAPEUTICS
(2021)