Morphogen gradient reconstitution reveals Hedgehog pathway design principles
Li, P., Markson, J. S., Wang, S., Chen, S., Vachharajani, V., Elowitz, M. B.
American Association for the Advancement of Science (AAAS)
Published 2018
American Association for the Advancement of Science (AAAS)
Published 2018
| Publication Date: |
2018-05-04
|
|---|---|
| Publisher: |
American Association for the Advancement of Science (AAAS)
|
| Print ISSN: |
0036-8075
|
| Electronic ISSN: |
1095-9203
|
| Topics: |
Biology
Chemistry and Pharmacology
Geosciences
Computer Science
Medicine
Natural Sciences in General
Physics
|
| Keywords: |
Development, Engineering
|
| Published by: |
| _version_ | 1836398918618841088 |
|---|---|
| autor | Li, P., Markson, J. S., Wang, S., Chen, S., Vachharajani, V., Elowitz, M. B. |
| beschreibung | In developing tissues, cells estimate their spatial position by sensing graded concentrations of diffusible signaling proteins called morphogens. Morphogen-sensing pathways exhibit diverse molecular architectures, whose roles in controlling patterning dynamics and precision have been unclear. In this work, combining cell-based in vitro gradient reconstitution, genetic rewiring, and mathematical modeling, we systematically analyzed the distinctive architectural features of the Sonic Hedgehog pathway. We found that the combination of double-negative regulatory logic and negative feedback through the PTCH receptor accelerates gradient formation and improves robustness to variation in the morphogen production rate compared with alternative designs. The ability to isolate morphogen patterning from concurrent developmental processes and to compare the patterning behaviors of alternative, rewired pathway architectures offers a powerful way to understand and engineer multicellular patterning. |
| citation_standardnr | 6251056 |
| datenlieferant | ipn_articles |
| feed_id | 25 |
| feed_publisher | American Association for the Advancement of Science (AAAS) |
| feed_publisher_url | http://www.aaas.org/ |
| insertion_date | 2018-05-04 |
| journaleissn | 1095-9203 |
| journalissn | 0036-8075 |
| publikationsjahr_anzeige | 2018 |
| publikationsjahr_facette | 2018 |
| publikationsjahr_intervall | 7984:2015-2019 |
| publikationsjahr_sort | 2018 |
| publisher | American Association for the Advancement of Science (AAAS) |
| quelle | Science |
| relation | http://science.sciencemag.org/cgi/content/short/360/6388/543?rss=1 |
| schlagwort | Development, Engineering |
| search_space | articles |
| shingle_author_1 | Li, P., Markson, J. S., Wang, S., Chen, S., Vachharajani, V., Elowitz, M. B. |
| shingle_author_2 | Li, P., Markson, J. S., Wang, S., Chen, S., Vachharajani, V., Elowitz, M. B. |
| shingle_author_3 | Li, P., Markson, J. S., Wang, S., Chen, S., Vachharajani, V., Elowitz, M. B. |
| shingle_author_4 | Li, P., Markson, J. S., Wang, S., Chen, S., Vachharajani, V., Elowitz, M. B. |
| shingle_catch_all_1 | Morphogen gradient reconstitution reveals Hedgehog pathway design principles Development, Engineering In developing tissues, cells estimate their spatial position by sensing graded concentrations of diffusible signaling proteins called morphogens. Morphogen-sensing pathways exhibit diverse molecular architectures, whose roles in controlling patterning dynamics and precision have been unclear. In this work, combining cell-based in vitro gradient reconstitution, genetic rewiring, and mathematical modeling, we systematically analyzed the distinctive architectural features of the Sonic Hedgehog pathway. We found that the combination of double-negative regulatory logic and negative feedback through the PTCH receptor accelerates gradient formation and improves robustness to variation in the morphogen production rate compared with alternative designs. The ability to isolate morphogen patterning from concurrent developmental processes and to compare the patterning behaviors of alternative, rewired pathway architectures offers a powerful way to understand and engineer multicellular patterning. Li, P., Markson, J. S., Wang, S., Chen, S., Vachharajani, V., Elowitz, M. B. American Association for the Advancement of Science (AAAS) 0036-8075 00368075 1095-9203 10959203 |
| shingle_catch_all_2 | Morphogen gradient reconstitution reveals Hedgehog pathway design principles Development, Engineering In developing tissues, cells estimate their spatial position by sensing graded concentrations of diffusible signaling proteins called morphogens. Morphogen-sensing pathways exhibit diverse molecular architectures, whose roles in controlling patterning dynamics and precision have been unclear. In this work, combining cell-based in vitro gradient reconstitution, genetic rewiring, and mathematical modeling, we systematically analyzed the distinctive architectural features of the Sonic Hedgehog pathway. We found that the combination of double-negative regulatory logic and negative feedback through the PTCH receptor accelerates gradient formation and improves robustness to variation in the morphogen production rate compared with alternative designs. The ability to isolate morphogen patterning from concurrent developmental processes and to compare the patterning behaviors of alternative, rewired pathway architectures offers a powerful way to understand and engineer multicellular patterning. Li, P., Markson, J. S., Wang, S., Chen, S., Vachharajani, V., Elowitz, M. B. American Association for the Advancement of Science (AAAS) 0036-8075 00368075 1095-9203 10959203 |
| shingle_catch_all_3 | Morphogen gradient reconstitution reveals Hedgehog pathway design principles Development, Engineering In developing tissues, cells estimate their spatial position by sensing graded concentrations of diffusible signaling proteins called morphogens. Morphogen-sensing pathways exhibit diverse molecular architectures, whose roles in controlling patterning dynamics and precision have been unclear. In this work, combining cell-based in vitro gradient reconstitution, genetic rewiring, and mathematical modeling, we systematically analyzed the distinctive architectural features of the Sonic Hedgehog pathway. We found that the combination of double-negative regulatory logic and negative feedback through the PTCH receptor accelerates gradient formation and improves robustness to variation in the morphogen production rate compared with alternative designs. The ability to isolate morphogen patterning from concurrent developmental processes and to compare the patterning behaviors of alternative, rewired pathway architectures offers a powerful way to understand and engineer multicellular patterning. Li, P., Markson, J. S., Wang, S., Chen, S., Vachharajani, V., Elowitz, M. B. American Association for the Advancement of Science (AAAS) 0036-8075 00368075 1095-9203 10959203 |
| shingle_catch_all_4 | Morphogen gradient reconstitution reveals Hedgehog pathway design principles Development, Engineering In developing tissues, cells estimate their spatial position by sensing graded concentrations of diffusible signaling proteins called morphogens. Morphogen-sensing pathways exhibit diverse molecular architectures, whose roles in controlling patterning dynamics and precision have been unclear. In this work, combining cell-based in vitro gradient reconstitution, genetic rewiring, and mathematical modeling, we systematically analyzed the distinctive architectural features of the Sonic Hedgehog pathway. We found that the combination of double-negative regulatory logic and negative feedback through the PTCH receptor accelerates gradient formation and improves robustness to variation in the morphogen production rate compared with alternative designs. The ability to isolate morphogen patterning from concurrent developmental processes and to compare the patterning behaviors of alternative, rewired pathway architectures offers a powerful way to understand and engineer multicellular patterning. Li, P., Markson, J. S., Wang, S., Chen, S., Vachharajani, V., Elowitz, M. B. American Association for the Advancement of Science (AAAS) 0036-8075 00368075 1095-9203 10959203 |
| shingle_title_1 | Morphogen gradient reconstitution reveals Hedgehog pathway design principles |
| shingle_title_2 | Morphogen gradient reconstitution reveals Hedgehog pathway design principles |
| shingle_title_3 | Morphogen gradient reconstitution reveals Hedgehog pathway design principles |
| shingle_title_4 | Morphogen gradient reconstitution reveals Hedgehog pathway design principles |
| timestamp | 2025-06-30T23:34:42.834Z |
| titel | Morphogen gradient reconstitution reveals Hedgehog pathway design principles |
| titel_suche | Morphogen gradient reconstitution reveals Hedgehog pathway design principles |
| topic | W V TE-TZ SQ-SU WW-YZ TA-TD U |
| uid | ipn_articles_6251056 |