ANR5, an FGF Target Gene Product, Regulates Gastrulation in Xenopus

Abstract

Gastrulation is a morphogenetic process in which tightly coordinated cell and tissue movements establish the three germ layers (ectoderm, mesoderm, and endoderm) to define the anterior-to-posterior embryonic organization [1]. To elicit this movement, cells modulate membrane protrusions and undergo dynamic cell interactions. Here we report that ankyrin repeats domain protein 5 (xANR5), a novel FGF target gene product, regulates cell-protrusion formation and tissue separation, a process that develops the boundary between the ectoderm and mesoderm [2, 3], during Xenopus gastrulation. Loss of xANR5 function by antisense morpholino oligonucleotide (MO) caused a short trunk and spina bifida without affecting mesodermal gene expressions. xANR5-MO also blocked elongation of activin-treated animal caps (ACs) and tissue separation. The dorsal cells of xANR5-MO-injected embryos exhibited markedly reduced membrane protrusions, which could be restored by coinjecting active Rho. Active Rho also rescued the xANR5-MO-inhibited tissue separation. We further demonstrated that xANR5 interacted physically and functionally with paraxial protocadherin (PAPC), which has known functions in cell-sorting behavior, tissue separation, and gastrulation cell movements [4-6], to regulate early morphogenesis. Our findings reveal for the first time that xANR5 acts through Rho to regulate gastrulation and is an important cytoplasmic partner of PAPC, whose cytoplasmic partner was previously unknown.

Xenopus Paraxial Protocadherin regulates morphogenesis by antagonizing Sprouty

“…As a result, Dsh and PKC␦ are not localized to the plasma membrane and RhoA is not activated. Recently, it was reported that Xenopus ANR5 protein, which can modulate gastrulation movements, interacts with xPAPC, corroborating the role of PAPC in intracellular signaling (Chung et al 2007). Our results presented here show that gastrulation movements can be modulated by sequestration of the inhibitor Spry by the cytoplasmic domain of xPAPC.…”

Maternal-zygotic medaka mutants forfgfr1reveal its essential role in the migration of the axial mesoderm but not the lateral mesoderm

“…Examples of this include the overexpression of Xsprouty2, a negative regulator of Fgf signaling (Nutt et al, 2001), and the knockdowns of neurotrophin receptor homolog (NRH) and ankyrin repeat domain protein 5 (Anr5), both Fgf downstream targets (Chung et al, 2005;Chung et al, 2007), which result in the inhibition of cell movement during convergent extension. In addition, chimeric analyses of the Fgfr1-knockout mouse have shown that these mutant cells fail to move away from the primitive streak (Ciruna and Rossant, 2001;Ciruna et al, 1997).…”

Cadherins in Brain Morphogenesis and Wiring

“…It has been shown that PAPC is involved in convergence and extension movements during gastrulation via two independent pathways, i.e., the Frizzled-7 PCP signaling pathway and Ccadherin-mediated adhesion (53,167,369,380). In addition, ankyrin repeats-domain protein-5 (ANR5) binds to the cytoplasmic domain of PAPC and regulates gastrulation (58). Moreover, PAPC forms a complex with FLRT3 and C-cadherin, and PAPC controls C-cadherin-mediated adhesion by regulating FRT3 activity via GTPase RND1 (54).…”