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Fascin1-Dependent Filopodia are Required for Directional Migration of a Subset of Neural Crest Cells


During vertebrate embryogenesis, neural crest (NC) cells migrate extensively along stereotypical migration routes and differentiate into diverse derivatives, including the craniofacial skeleton and peripheral nervous system. While defects in NC migration underlie many human birth defects and may be coopted during cancer metastasis, the genetic pathways controlling directional NC migration remain incompletely understood. Filopodia protrusions are thought to act as “cellular antennae” that explore the environment for directional cues to ensure NC cells reach their correct location. To test this idea, we generated zebrafish fascin1a (fscn1a) mutants that have severe loss of filopodia. Surprisingly, we found that most NC cells migrate to their correct locations without robust filopodial protrusions. We found that fscn1a embryos have directional migration defects in a subset of NC cells, resulting in loss of specific craniofacial elements and peripheral neurons. Interestingly, these defects were only observed in ∼20% of fscn1a embryos, but were significantly enhanced by partial loss of the chemokine receptor Cxcr4a or disruption of the localized expression of its ligand Cxcl12b. Our data show that subsets of skeletal and neurogenic NC cells require filopodia to migrate and that fscn1a-dependent filopodia cooperate with chemokine signaling to promote directional migration of a subset of NC cells.


Vyšlo v časopise: Fascin1-Dependent Filopodia are Required for Directional Migration of a Subset of Neural Crest Cells. PLoS Genet 11(1): e32767. doi:10.1371/journal.pgen.1004946
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004946

Souhrn

During vertebrate embryogenesis, neural crest (NC) cells migrate extensively along stereotypical migration routes and differentiate into diverse derivatives, including the craniofacial skeleton and peripheral nervous system. While defects in NC migration underlie many human birth defects and may be coopted during cancer metastasis, the genetic pathways controlling directional NC migration remain incompletely understood. Filopodia protrusions are thought to act as “cellular antennae” that explore the environment for directional cues to ensure NC cells reach their correct location. To test this idea, we generated zebrafish fascin1a (fscn1a) mutants that have severe loss of filopodia. Surprisingly, we found that most NC cells migrate to their correct locations without robust filopodial protrusions. We found that fscn1a embryos have directional migration defects in a subset of NC cells, resulting in loss of specific craniofacial elements and peripheral neurons. Interestingly, these defects were only observed in ∼20% of fscn1a embryos, but were significantly enhanced by partial loss of the chemokine receptor Cxcr4a or disruption of the localized expression of its ligand Cxcl12b. Our data show that subsets of skeletal and neurogenic NC cells require filopodia to migrate and that fscn1a-dependent filopodia cooperate with chemokine signaling to promote directional migration of a subset of NC cells.


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