Pitx2c orchestrates embryonic axis extension via mesendodermal cell migration.

Abstract

Pitx2c, a homeodomain transcription factor, is classically known for its left-right patterning role. However, an early wave of <i>pitx2</i> expression occurs at the onset of gastrulation in several species, indicating a possible earlier role that remains relatively unexplored. Here we show that in zebrafish, maternal-zygotic (MZ) <i>pitx2c</i> mutants exhibit a shortened body axis indicative of convergence and extension (CE) defects. Live imaging reveals that MZ<i>pitx2c</i> mutants display less persistent mesendodermal migration during late stages of gastrulation. Transplant data indicate that Pitx2c functions cell non-autonomously to regulate this cell behavior by modulating cell shape and protrusive activity. Using transcriptomic analyses and candidate gene approaches, we identify transcriptional changes in components of the chemokine-ECM-integrin dependent mesendodermal migration network. Together, our results define pathways downstream of Pitx2c that are required during early embryogenesis and reveal novel functions for Pitx2c as a regulator of morphogenesis.