Met regulates endoderm migration in zebrafish

Abstract

Cells can employ different modes of migration, switching between them depending on context. However, how migration modes are determined remains incompletely understood. The mode of migration depends not only on external signals and guidance cues but also on which cell surface receptors a cell expresses. Receptor tyrosine kinases (RTKs) are central mediators of many processes including cell migration, yet whether RTK signaling mediates shifts in migratory behavior in vivo remains unclear. Here, we show that the RTK Met promotes persistent, directional migration of endodermal cells during gastrulation in zebrafish. met is broadly expressed across migrating endoderm, and pharmacological inhibition or genetic loss of its function delays endoderm convergence. Quantitative live imaging and cell tracking reveal that loss of Met reduces displacement and persistence without substantially affecting velocity, indicating that Met promotes directional migration rather than motility per se. Although Met is canonically activated by hepatocyte growth factor (Hgf), expression of hgfa and hgfb during gastrulation is spatially restricted and temporally limited. Consistent with this, genetic loss of Hgf function indicates that it is dispensable for endoderm convergence and migration. Together, these findings identify Met as a regulator of migratory persistence during endoderm convergence and suggest a ligand-independent mode of RTK function in the regulation of cell behavior during development. HighlightsO_LIMet promotes directional migration of endoderm cells during convergence. C_LIO_LILoss of Met delays convergence by reducing cell displacement and persistence without affecting velocity. C_LIO_LIHgf signaling is dispensable for endoderm convergence despite being the canonical Met ligand. C_LI