Zebrafish trilobite identifies new roles for Strabismus in gastrulation and neuronal movements

Abstract

Embryonic morphogenesis is driven by a suite of cell behaviours, including coordinated shape changes, cellular rearrangements and individual cell migrations, whose molecular determinants are largely unknown. In the zebrafish, Dani rerio, trilobite mutant embryos have defects in gastrulation movements and posterior migration of hindbrain neurons. Here, we have used positional cloning to demonstrate that trilobite mutations disrupt the transmembrane protein Strabismus (Stbm)/Van Gogh (Vang), previously associated with planar cell polarity (PCP) in Drosophila melanogaster, and PCP and canonical Wnt/beta-catenin signalling in vertebrates. Our genetic and molecular analyses argue that during gastrulation, trilobite interacts with the PCP pathway without affecting canonical Wnt signalling. Furthermore, trilobite may regulate neuronal migration independently of PCP molecules. We show that trilobite mediates polarization of distinct movement behaviours. During gastrulation convergence and extension movements, trilobite regulates mediolateral cell polarity underlying effective intercalation and directed dorsal migration at increasing velocities. In the hindbrain, trilobite controls effective migration of branchiomotor neurons towards posterior rhombomeres. Mosaic analyses show trilobite functions cell-autonomously and non-autonomously in gastrulae and the hindbrain. We propose Trilobite/Stbm mediates cellular interactions that confer directionality on distinct movements during vertebrate embryogenesis.

Turning heads: Development of vertebrate branchiomotor neurons

“…In contrast to the well-documented roles for environmental cues in nVII neuron migration described above (Studer, 2001;Jessen et al, 2002;Carreira-Barbosa et al, 2003), much less is known about mechanisms that act within nVII neurons to mediate tangential migration. In mouse, genes encoding various axon guidance and cell adhesion molecules are expressed in nVII motor neurons during specific migratory phases (Garel et al, 2000;Muller et al, 2003).…”

“…Genetic mosaic analysis shows that wild-type nVII neurons are unable to migrate caudally in a mutant environment, and conversely, tri mutant motor neurons frequently, but not always, migrate in a wild-type environment, demonstrating a strong non-cell autonomous role for Trilobite in tangential migration of nVII neurons (Jessen et al, 2002). Trilobite encodes a transmembrane protein Strabismus (Jessen et al, 2002;Park and Moon, 2002), which is a key component of the noncanonical Wingless/Wnt signaling pathway that mediates planar cell polarity (PCP) in Drosophila and gastrulation-associated cell movements in vertebrates (reviewed in Tada et al, 2002;Tree et al, 2002;Veeman et al, 2003). High-resolution analysis of migrating motor neurons suggests that tri mutant motor neurons have lost the ability either to generate protusions in a polarized manner or to stably maintain polar protusions (Jessen et al, 2002).…”

“…Trilobite encodes a transmembrane protein Strabismus (Jessen et al, 2002;Park and Moon, 2002), which is a key component of the noncanonical Wingless/Wnt signaling pathway that mediates planar cell polarity (PCP) in Drosophila and gastrulation-associated cell movements in vertebrates (reviewed in Tada et al, 2002;Tree et al, 2002;Veeman et al, 2003). High-resolution analysis of migrating motor neurons suggests that tri mutant motor neurons have lost the ability either to generate protusions in a polarized manner or to stably maintain polar protusions (Jessen et al, 2002). Because trilobite is expressed ubiquitously in the hindbrain during the period of nVII neuron migration, the challenge will be to unravel how the expression of a transmembrane protein on surrounding cells can affect the ability of migrating motor neurons to move in a directed manner.…”

Controlled levels of canonical Wnt signaling are required for neural crest migration

“…What's more, inhibition of Wnt11 through overexpression of dominant-negative construct leads to a complete inhibition of NC migration (De Calisto et al, 2005). In zebrafish, mutations of Stbm/trilobite (Jessen et al, 2002), Wnt11/silberblick (Heisenberg et al, 2000) or Wnt5/pipetail also causes a defect in directional NC migration (Rauch et al, 1997;Matthews et al, 2008). Injections of dominant-negative Dishevelled inhibiting PCP signaling but not canonical Wnt signaling inhibit migration of NC cells in Xenopus (De Calisto et al, 2005) and severely disrupt the directional migration of NC cells in zebrafish (Matthews et al, 2008).…”

JNK and ROKα function in the noncanonical Wnt/RhoA signaling pathway to regulate Xenopus convergent extension movements

“…Furthermore, the specific domains of Dsh (Wharton, 2003) required for PCP signaling in CE movements during vertebrate gastrulation (Djiane et al, 2000;Heisenberg et al, 2000;Medina et al, 2000;Tada and Smith, 2000;Wallingford et al, 2000) are identical to those required in Drosophila (Axelrod et al, 1998;Boutros et al, 1998;Boutros and Mlodzik, 1999). In addition, CE movements in both Xenopus and zebrafish are controlled by the core PCP genes, including RhoA/Rac1 (Habas et al, 2001(Habas et al, , 2003Tahinci and Symes, 2003), JNK (Yamanaka et al, 2002), Rho-associated kinase-2 (ROK2, Marlow et al, 2002), Strabismus (Stbm, Darken et al, 2002;Goto and Keller, 2002;Jessen et al, 2002;Park and Moon, 2002), and Prickle (Takeuchi et al, 2003;Veeman et al, 2003a).…”