Meteorins regulate the formation of the left-right organizer and the establishment of vertebrate body asymmetry
While the exterior of vertebrate bodies appears bilaterally symmetrical, internal organ positioning and morphology frequently exhibit left-right (L-R) asymmetries. In several vertebrates, including human, mouse, frog, and zebrafish, left-right symmetry-breaking during embryonic development is initia...
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eLife Sciences Publications Ltd
2025-08-01
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| Online Access: | https://elifesciences.org/articles/105430 |
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| author | Fanny Eggeler Jonathan Boulanger-Weill Flavia De Santis Laura Belleri Karine Duroure Thomas O Auer Shahad Albadri Filippo Del Bene |
| author_facet | Fanny Eggeler Jonathan Boulanger-Weill Flavia De Santis Laura Belleri Karine Duroure Thomas O Auer Shahad Albadri Filippo Del Bene |
| author_sort | Fanny Eggeler |
| collection | DOAJ |
| description | While the exterior of vertebrate bodies appears bilaterally symmetrical, internal organ positioning and morphology frequently exhibit left-right (L-R) asymmetries. In several vertebrates, including human, mouse, frog, and zebrafish, left-right symmetry-breaking during embryonic development is initiated by a ciliated organ called the Node or left-right organizer. Within the Node, a leftward flow of extraembryonic fluid named the Nodal flow mediates the asymmetric expressions of Nodal factors. Although downstream Nodal pathway components leading to the establishment of the embryonic left-right axis are well known, less is known about the development and formation of the embryonic Node itself. Here, we reveal a novel role for the Meteorin protein family in the establishment of the left-right axis and in the formation of Kupffer’s vesicle, the Node equivalent structure in zebrafish. We show that the genetic inactivation of each or all three members of the zebrafish Meteorin family (metrn, metrn-like a, and metrn-like b) leads to defects in properties of the Kupffer’s vesicle, caused by impaired assembly and migration of the Kupffer’s vesicle forming dorsal forerunner cells. In addition, we demonstrate that Meteorins genetically interact with integrins ItgαV and Itgβ1b, regulating the dorsal forerunner cell clustering, and that meteorins loss-of-function results in disturbed Nodal factor expression and consequently in randomized or symmetric heart looping and jogging. These results identify a new role for the Meteorin protein family in the left-right asymmetry patterning during embryonic vertebrate development. |
| format | Article |
| id | doaj-art-ebe8a96e813049f9a3f51555cf19a5fb |
| institution | Kabale University |
| issn | 2050-084X |
| language | English |
| publishDate | 2025-08-01 |
| publisher | eLife Sciences Publications Ltd |
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| series | eLife |
| spelling | doaj-art-ebe8a96e813049f9a3f51555cf19a5fb2025-08-20T03:34:10ZengeLife Sciences Publications LtdeLife2050-084X2025-08-011410.7554/eLife.105430Meteorins regulate the formation of the left-right organizer and the establishment of vertebrate body asymmetryFanny Eggeler0https://orcid.org/0009-0001-6803-1984Jonathan Boulanger-Weill1https://orcid.org/0000-0002-1580-0778Flavia De Santis2https://orcid.org/0000-0002-0988-6560Laura Belleri3https://orcid.org/0009-0001-5475-7821Karine Duroure4https://orcid.org/0000-0002-5959-569XThomas O Auer5https://orcid.org/0000-0003-3442-0567Shahad Albadri6https://orcid.org/0000-0002-3243-7018Filippo Del Bene7https://orcid.org/0000-0001-8551-2846Sorbonne Université, INSERM, CNRS, Institut de la Vision, Paris, FranceSorbonne Université, INSERM, CNRS, Institut de la Vision, Paris, FranceInstitut Curie, PSL Research University, Paris, France; ZeClinics SL. Sant Feliu de Llobregat, Barcelona, SpainSorbonne Université, INSERM, CNRS, Institut de la Vision, Paris, FranceSorbonne Université, INSERM, CNRS, Institut de la Vision, Paris, FranceInstitut Curie, PSL Research University, Paris, France; Department of Biology, University of Fribourg, Fribourg, SwitzerlandSorbonne Université, INSERM, CNRS, Institut de la Vision, Paris, FranceSorbonne Université, INSERM, CNRS, Institut de la Vision, Paris, FranceWhile the exterior of vertebrate bodies appears bilaterally symmetrical, internal organ positioning and morphology frequently exhibit left-right (L-R) asymmetries. In several vertebrates, including human, mouse, frog, and zebrafish, left-right symmetry-breaking during embryonic development is initiated by a ciliated organ called the Node or left-right organizer. Within the Node, a leftward flow of extraembryonic fluid named the Nodal flow mediates the asymmetric expressions of Nodal factors. Although downstream Nodal pathway components leading to the establishment of the embryonic left-right axis are well known, less is known about the development and formation of the embryonic Node itself. Here, we reveal a novel role for the Meteorin protein family in the establishment of the left-right axis and in the formation of Kupffer’s vesicle, the Node equivalent structure in zebrafish. We show that the genetic inactivation of each or all three members of the zebrafish Meteorin family (metrn, metrn-like a, and metrn-like b) leads to defects in properties of the Kupffer’s vesicle, caused by impaired assembly and migration of the Kupffer’s vesicle forming dorsal forerunner cells. In addition, we demonstrate that Meteorins genetically interact with integrins ItgαV and Itgβ1b, regulating the dorsal forerunner cell clustering, and that meteorins loss-of-function results in disturbed Nodal factor expression and consequently in randomized or symmetric heart looping and jogging. These results identify a new role for the Meteorin protein family in the left-right asymmetry patterning during embryonic vertebrate development.https://elifesciences.org/articles/105430Meteorinleft-right asymmetryembryonic development |
| spellingShingle | Fanny Eggeler Jonathan Boulanger-Weill Flavia De Santis Laura Belleri Karine Duroure Thomas O Auer Shahad Albadri Filippo Del Bene Meteorins regulate the formation of the left-right organizer and the establishment of vertebrate body asymmetry eLife Meteorin left-right asymmetry embryonic development |
| title | Meteorins regulate the formation of the left-right organizer and the establishment of vertebrate body asymmetry |
| title_full | Meteorins regulate the formation of the left-right organizer and the establishment of vertebrate body asymmetry |
| title_fullStr | Meteorins regulate the formation of the left-right organizer and the establishment of vertebrate body asymmetry |
| title_full_unstemmed | Meteorins regulate the formation of the left-right organizer and the establishment of vertebrate body asymmetry |
| title_short | Meteorins regulate the formation of the left-right organizer and the establishment of vertebrate body asymmetry |
| title_sort | meteorins regulate the formation of the left right organizer and the establishment of vertebrate body asymmetry |
| topic | Meteorin left-right asymmetry embryonic development |
| url | https://elifesciences.org/articles/105430 |
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