Rapgef1 paralog-mediated regulation of Wnt/β-catenin signaling orchestrates early embryo tissue patterning and morphogenesis.

RAPGEF1, a guanine nucleotide exchange factor, regulates signaling and cytoskeletal dynamics in mammalian cells, yet its role in development remains unclear as Rapgef1 null mouse embryos do not survive beyond implantation. We demonstrate that zebrafish rapgef1 is maternally expressed, and its paralogs, rapgef1a and rapgef1b, exhibit tissue and developmental stage-specific splicing. Disruption of rapgef1b caused brain and somite defects, impaired cranial neural crest specification, and microcephaly-like phenotypes, uncovering its previously uncharacterized functions in morphogenesis and tissue patterning. Transcriptomic analyses and differential gene expression provide fresh insights into the developmental functions of rapgef1b in presomitic mesoderm and somitogenesis by modulating the Wnt/β catenin signaling. Rapgef1b deficient embryos also showed spindle pole disorganization and chromosome mis-congression, linking Rapgef1 to centrosome-mediated mitotic fidelity. Together, our findings identify Rapgef1b as a key regulator of neural crest development, mesodermal morphogenesis, and early mitoses, highlighting its tissue-specific functions during vertebrate embryogenesis.