Dual roles of zygotic and maternal Scribble1 in neural migration and convergent extension movements in zebrafish embryos

Abstract

In the developing vertebrate hindbrain, the characteristic trajectory of the facial (nVII) motor nerve is generated by caudal migration of the nVII motor neurons. The nVII motor neurons originate in rhombomere (r) 4, and migrate caudally into r6 to form the facial motor nucleus. In this study,using a transgenic zebrafish line that expresses green fluorescent protein(GFP) in the cranial motor neurons, we isolated two novel mutants, designated landlocked (llk) and off-road (ord), which both show highly specific defects in the caudal migration of the nVII motor neurons. We show that the landlocked locus contains the gene scribble1 (scrb1), and that its zygotic expression is required for migration of the nVII motor neurons mainly in a non cell-autonomous manner. Taking advantage of the viability of the llkmutant embryos, we found that maternal expression of scrb1 is required for convergent extension (CE) movements during gastrulation. Furthermore, we show a genetic interaction between scrb1 and trilobite(tri)/strabismus(stbm) in CE. The dual roles of the scrb1 gene in both neuronal migration and CE provide a novel insight into the underlying mechanisms of cell movement in vertebrate development.

The tumour-suppressor Scribble dictates cell polarity during directed epithelial migration: regulation of Rho GTPase recruitment to the leading edge

“…The role of Scribble as a highly conserved regulator of all types of cell motility is further highlighted by two recent publications showing that Scribble controls the migration of nonepithelial cell types, namely motor neurons in zebrafish and murine T lymphocytes (Ludford-Menting et al, 2005;Wada et al, 2005). In zebrafish, zygotic mutation of scribble in the landlocked (llk) mutant or Scribble knockdown results in failure of nVII motor neuron migration and loss of maternal Scribble expression causes defects in convergent extension during embryogenesis (Wada et al, 2005). Knockdown of Scribble in murine MD45T lymphocytes results in a profound defect in cell polarity and a loss of uropod formation.…”

Asymmetric Localization of Vangl2 and Fz3 Indicate Novel Mechanisms for Planar Cell Polarity in Mammals

“…A recent paper showed the existence of an interaction between Drosophila PALS-1 associated tight junction protein, a protein from the apical marginal region junction, and fz1 in Drosophila eye, suggesting that molecules necessary for apical-basal polarity and planar polarity can interact (Djiane et al, 2005). Another recent paper analyzed the interactions of trilobite (tri)/stbm (a zebrafish allele of Vangl2) and scrb1 (Wada et al, 2005). The authors suggest that the two proteins could form a functional complex in which tri/stbm may be required for localization of scrb1 to the specific site of the membrane in which they are anchored and function.…”

Zebrafish Prickle1b mediates facial branchiomotor neuron migration via a farnesylation-dependent nuclear activity

“…Among many proteins known to regulate this migration in zebrafish are several core planar cell polarity (PCP) components (reviewed by Wada and Okamoto, 2009a;Wada and Okamoto, 2009b). These molecules include Vang-like 2 (Vangl2) (Jessen et al, 2002;Bingham et al, 2002); Frizzled 3a (Fzd3a), Cadherin EGF LAG seven-pass G-type receptor 1a (Celsr1a), Celsr1b, Celsr2 (Wada et al, 2006); Scribble 1 (Scrib) (Wada et al, 2005); Prickle1a (Pk1a) (Carreira-Barbosa et al, 2003); and Pk1b (Rohrschneider et al, 2007). Several characteristics of Pk1b make it unique among these PCP components.…”