A novel role of Furry in early vertebrate development: regulation of convergent forces during gastrulation

CERVINO, AILEN; CIRIO, MARIA CECILIA

Taller; IV Taller de Biología Celular y del Desarrollo; 2018

The morphogenetic events that take place during gastrulation establish the embryonic basic body plan. These key processes are initially executed and coordinated by a dynamic group of cells called ?the Spemann organizer? in amphibians. The molecular mechanisms that regulate formation and maintenance of the organizer and the course of gastrulation are focus of numerous studies given the significance of these events for normal development.Furry (Fry) gene encodes a large, evolutionarily conserved protein with a wide variety of functions, mostly associated with maintenance of cytoskeleton structure, cell-polarization and morphogenesis. In Xenopus, dorsal depletion of Fry produces shortening of the dorsal axis and interferes with head formation, a phenotype that is frequently associated with gastrulation defects and/or incorrect progenitor cells specification.To study the role of Fry in early development we injected a specific morpholino in Xenopus embryos. Dorsal depletion of Fry results in a reduced expression domain of the organizer genes goosecoid, chordin and otx2, indicating that Fry is required for organizer formation.Fry-depleted embryos also exhibit blastopore closure defects and chordamesoderm elongation impairment, gauged by not expression domain. Since convergent-extension (CE) movement conducted by dorsal mesoderm extends the body axis and aid blastopore closure, we evaluated this morphogenetic behavior by performing dorsal gastrula explants. As expected, dorsal explants from fry-depleted embryos do not extend, demonstrating Fry is involved in CE. Interestingly, ventral depletion of Fry, which has no influence in CE, also causes gastrulation defects suggesting that Fry is important for general convergent forces during gastrulation. Moreover, dorsal expression of a short version of Fry called FD+LZ does not perturb CE but compromises gastrulation. Since the gastrulation-CE phenotypes we observed resemble a classical Planar Cell Polarity perturbation, we study the expression pattern of several genes involved in this signaling pathway and found no alterations in Fry-depleted embryos. Together, our results suggest that Fry has an important role in early development: it is involved in the establishment of the dorsal organizer and in the correct execution of morphogenetic movements, especially dorsal mesoderm CE behavior. Nevertheless, future experiments are required to elucidate the cellular and molecular mechanisms in which Fry is involved.