Ciliary Hedgehog signaling patterns the digestive system to generate mechanical forces driving elongation
| Autor: | Yang, Ying, Paivinen, Pekka, Xie, Chang, Krup, Alexis Leigh, Makela, Tomi P., Mostov, Keith E., Reiter, Jeremy F. |
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| Přispěvatelé: | Helsinki Institute of Life Science HiLIFE, Digital Precision Cancer Medicine (iCAN), Department of Biochemistry and Developmental Biology, Mäkelä Lab, HUS Helsinki and Uusimaa Hospital District |
| Rok vydání: | 2021 |
| Předmět: |
Cell biology
Science Myocytes Smooth Muscle REQUIREMENT General Physics and Astronomy Protein Serine-Threonine Kinases Article General Biochemistry Genetics and Molecular Biology Mesoderm Mice 03 medical and health sciences Smooth Muscle Developmental biology Animals Hedgehog Proteins Cilia Cell Proliferation 030304 developmental biology Myocytes 0303 health sciences Multidisciplinary INTESTINAL-CELL KINASE 030302 biochemistry & molecular biology PROLIFERATION Muscle Smooth General Chemistry MUSCLE SMOOTH APOPTOSIS Gastrointestinal Tract CALCIUM SENSITIZATION MORPHOGENESIS GROWTH 1182 Biochemistry cell and molecular biology Muscle YAP Smooth Digestive Diseases Signal Transduction |
| Zdroj: | Nature communications, vol 12, iss 1 Nature Communications Nature Communications, Vol 12, Iss 1, Pp 1-14 (2021) |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/s41467-021-27319-z |
| Popis: | How tubular organs elongate is poorly understood. We found that attenuated ciliary Hedgehog signaling in the gut wall impaired patterning of the circumferential smooth muscle and inhibited proliferation and elongation of developing intestine and esophagus. Similarly, ablation of gut-wall smooth muscle cells reduced lengthening. Disruption of ciliary Hedgehog signaling or removal of smooth muscle reduced residual stress within the gut wall and decreased activity of the mechanotransductive effector YAP. Removing YAP in the mesenchyme also reduced proliferation and elongation, but without affecting smooth muscle formation, suggesting that YAP interprets the smooth muscle-generated force to promote longitudinal growth. Additionally, we developed an intestinal culture system that recapitulates the requirements for cilia and mechanical forces in elongation. Pharmacologically activating YAP in this system restored elongation of cilia-deficient intestines. Thus, our results reveal that ciliary Hedgehog signaling patterns the circumferential smooth muscle to generate radial mechanical forces that activate YAP and elongate the gut. The mechanisms underlying tubular organ elongation remain poorly understood. Here, the authors show that primary cilia interpret Hedgehog signals to pattern the developing gut and that smooth muscle in the gut wall generates mechanical forces that direct longitudinal growth. |
| Databáze: | OpenAIRE |
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