Rgp1 Regulates Craniofacial Cartilage Development

Abstract

Rgp1 was previously identified as a component of a guanine nucleotide exchange factor complex to activate Rab6a-mediated Golgi-centric trafficking events. While the role of Rgp1 in protein trafficking has been examined in vitro and in yeast, the role of Rgp1 during vertebrate embryogenesis and protein trafficking in vivo is unknown. Using CRISPR-induced zebrafish rgp1 mutants, we found that Rgp1 is required for craniofacial cartilage development. We identified two phenotypes within chondrocytes composing the craniofacial cartilage, defects in collagen II secretion and an abnormal chondrocyte cell shape. We found that the two phenotypes are regulated through distinct pathways. Rab6a and Rab8a coordinate collagen II secretion from the Golgi to the plasma membrane, a process independent of cell shape. Meanwhile, Rab11a is critical for regulating chondrocyte cell shape development in Rgp1 mutant embryos. A better understanding of how Rgp1 regulates collagen II secretion and cell shape will shed light on processes that control the secretion of large cargoes in other tissues and the mechanisms by which cells change shape during development.