Deficiency of the HGF/Met pathway leads to thyroid dysgenesis by impeding late thyroid expansion
© 2024. The Author(s)..
The mechanisms of bifurcation, a key step in thyroid development, are largely unknown. Here we find three zebrafish lines from a forward genetic screening with similar thyroid dysgenesis phenotypes and identify a stop-gain mutation in hgfa and two missense mutations in met by positional cloning from these zebrafish lines. The elongation of the thyroid primordium along the pharyngeal midline was dramatically disrupted in these zebrafish lines carrying a mutation in hgfa or met. Further studies show that MAPK inhibitor U0126 could mimic thyroid dysgenesis in zebrafish, and the phenotypes are rescued by overexpression of constitutively active MEK or Snail, downstream molecules of the HGF/Met pathway, in thyrocytes. Moreover, HGF promotes thyrocyte migration, which is probably mediated by downregulation of E-cadherin expression. The delayed bifurcation of the thyroid primordium is also observed in thyroid-specific Met knockout mice. Together, our findings reveal that HGF/Met is indispensable for the bifurcation of the thyroid primordium during thyroid development mediated by downregulation of E-cadherin in thyrocytes via MAPK-snail pathway.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:15 |
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| Enthalten in: |
Nature communications - 15(2024), 1 vom: 11. Apr., Seite 3165 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Fang, Ya [VerfasserIn] |
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| Links: |
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| Themen: |
67256-21-7 |
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| Anmerkungen: |
Date Completed 15.04.2024 Date Revised 25.04.2024 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1038/s41467-024-47363-9 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM370943260 |
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| 245 | 1 | 0 | |a Deficiency of the HGF/Met pathway leads to thyroid dysgenesis by impeding late thyroid expansion |
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| 520 | |a © 2024. The Author(s). | ||
| 520 | |a The mechanisms of bifurcation, a key step in thyroid development, are largely unknown. Here we find three zebrafish lines from a forward genetic screening with similar thyroid dysgenesis phenotypes and identify a stop-gain mutation in hgfa and two missense mutations in met by positional cloning from these zebrafish lines. The elongation of the thyroid primordium along the pharyngeal midline was dramatically disrupted in these zebrafish lines carrying a mutation in hgfa or met. Further studies show that MAPK inhibitor U0126 could mimic thyroid dysgenesis in zebrafish, and the phenotypes are rescued by overexpression of constitutively active MEK or Snail, downstream molecules of the HGF/Met pathway, in thyrocytes. Moreover, HGF promotes thyrocyte migration, which is probably mediated by downregulation of E-cadherin expression. The delayed bifurcation of the thyroid primordium is also observed in thyroid-specific Met knockout mice. Together, our findings reveal that HGF/Met is indispensable for the bifurcation of the thyroid primordium during thyroid development mediated by downregulation of E-cadherin in thyrocytes via MAPK-snail pathway | ||
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| 700 | 1 | |a Wan, Jia-Ping |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Zheng |e verfasserin |4 aut | |
| 700 | 1 | |a Song, Shi-Yang |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Cao-Xu |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Liu |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Qian-Yue |e verfasserin |4 aut | |
| 700 | 1 | |a Yan, Chen-Yan |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Feng-Yao |e verfasserin |4 aut | |
| 700 | 1 | |a Lu, Sang-Yu |e verfasserin |4 aut | |
| 700 | 1 | |a Sun, Feng |e verfasserin |4 aut | |
| 700 | 1 | |a Han, Bing |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Shuang-Xia |e verfasserin |4 aut | |
| 700 | 1 | |a Dong, Mei |e verfasserin |4 aut | |
| 700 | 1 | |a Song, Huai-Dong |e verfasserin |4 aut | |
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