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

<div><p>Directional migration of neural crest (NC) cells is essential for patterning the vertebrate embryo, including the craniofacial skeleton. Extensive filopodial protrusions in NC cells are thought to sense chemo-attractive/repulsive signals that provide directionality. To test this hypothesis, we generated null mutations in zebrafish <i>fascin1a (fscn1a)</i>, which encodes an actin-bundling protein required for filopodia formation. Homozygous <i>fscn1a</i> zygotic null mutants have normal NC filopodia due to unexpected stability of maternal Fscn1a protein throughout NC development and into juvenile stages. In contrast, maternal/zygotic <i>fscn1a</i> null mutant embryos (<i>fscn1a MZ</i>) have severe loss of NC filopodia. However, only a subset of NC streams display migration defects, associated with selective loss of craniofacial elements and peripheral neurons. We also show that <i>fscn1a</i>-dependent NC migration functions through <i>cxcr4a/cxcl12b</i> chemokine signaling to ensure the fidelity of directional cell migration. These data show that <i>fscn1a</i>-dependent filopodia are required in a subset of NC cells to promote cell migration and NC derivative formation, and that perdurance of long-lived maternal proteins can mask essential zygotic gene functions during NC development.</p>