Notch signaling restricts FGF pathway activation in parapineal cells to promote their collective migration

Autor: Amir Al Oustah, Lu Wei, Myriam Roussigne, Patrick Blader
Přispěvatelé: Centre de biologie du développement (CBD), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre de Biologie Intégrative (CBI), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)
Rok vydání: 2019
Předmět:
QH301-705.5
Science
Cell
Notch signaling pathway
Context (language use)
[SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC]
FGF pathway
Fibroblast growth factor
General Biochemistry
Genetics and Molecular Biology
03 medical and health sciences
0302 clinical medicine
Cell Movement
medicine
Animals
Epithalamus
Gene Regulatory Networks
Biology (General)
Zebrafish
030304 developmental biology
0303 health sciences
collective cell migration
Receptors
Notch
General Immunology and Microbiology
biology
General Neuroscience
Embryogenesis
Gene Expression Regulation
Developmental
Cell Biology
General Medicine
left right asymmetry
biology.organism_classification
notch signaling
Cell biology
Fibroblast Growth Factors
[SDV.BDD.EO]Life Sciences [q-bio]/Development Biology/Embryology and Organogenesis
medicine.anatomical_structure
Medicine
Developmental biology
030217 neurology & neurosurgery
Signal Transduction
Research Article
Developmental Biology
Zdroj: eLife
eLife, eLife Sciences Publication, 2019, 8, pp.e46275. ⟨10.7554/eLife.46275⟩
eLife, Vol 8 (2019)
ISSN: 2050-084X
DOI: 10.7554/elife.46275
Popis: Coordinated migration of cell collectives is important during embryonic development and relies on cells integrating multiple mechanical and chemical cues. Recently, we described that focal activation of the FGF pathway promotes the migration of the parapineal in the zebrafish epithalamus. How FGF activity is restricted to leading cells in this system is, however, unclear. Here, we address the role of Notch signaling in modulating FGF activity within the parapineal. While Notch loss-of-function results in an increased number of parapineal cells activating the FGF pathway, global activation of Notch signaling decreases it; both contexts result in defects in parapineal migration and specification. Decreasing or increasing FGF signaling in a Notch loss-of-function context respectively rescues or aggravates parapineal migration defects without affecting parapineal cells specification. We propose that Notch signaling controls the migration of the parapineal through its capacity to restrict FGF pathway activation to a few leading cells.
eLife digest Many animal cells must move through the body from the place they are born to where they are needed, for example, when embryos are developing or wounds are healing. Often cells migrate in groups, which helps them to navigate and co-ordinate more effectively. Cells typically migrate by sensing different signals across large areas, and groups of cells communicate with each other to co-ordinate their migration. One group of cells that is studied to understand collective cell migration is found in the brain of the zebrafish. These cells are called parapineal cells and, in the developing fish, they move towards the left side of the brain under the influence of a signal called Fgf8. Although all parapineal cells can detect Fgf8, only those at the front of the migrating group respond to the signal. These are the cells that lead the migration. It was previously unclear how the capability of responding to Fgf8 is limited to only a few parapineal cells to ensure they all migrate correctly. By studying parapineal cell migration, Wei et al. identified a different signaling system called Notch as a regulator of cell migration. When Notch signaling activity is artificially increased in the brain, parapineal cells do not respond to Fgf8 as efficiently as when levels of Notch are normal. Conversely, the number of parapineal cells that respond to Fgf8 increases when Notch signaling is lost. In both cases, migration of parapineal cells is affected. Therefore, Wei et al. showed that changing the balance of Notch signaling in the zebrafish brain modifies the ability of parapineal cells to respond to Fgf8 signal and stops parapineal cells from migrating correctly. These results provide a general model for how cells migrate as a group. More studies are needed to see if similar mechanisms are involved in other examples of collective cell migration. This model of group migration could be applied to healthy processes such as embryonic development as well as examples of cell migration in illness such as cancer metastasis.
Databáze: OpenAIRE
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