Is there a better subject for time-lapse pho-tography than embryogenesis? By condens-ing the three-dimensional complexity ofdevelopment into a few seconds, movie-makers have shown the embryo to be ashape-changing marvel. In recent years,geneticists have begun to chip away at themolecular pathways that underlie morpho-genesis. Writing in Nature Cell Biology,Jason Jessen and colleagues1 describe thelatest progress in the genetic dissection ofthe embryonic cellular movements knownas convergent extension.

The vertebrate fertilized egg begins lifeas a sphere that soon becomes an elon-gated and visibly polar embryo. Thistransformation is powered in part by thestereotypical movements of a subset ofcells during gastrulation. These cells firstmigrate from lateral regions toward thedorsal midline (convergence), and thenintercalate between one another, therebynarrowing the assemblage of cells alongone axis and extending it along the per-pendicular axis (extension).

Recent evidence suggests that vertebrateorthologs of the Drosophila melanogaster

gene Strabismus (Stbm), encoding a trans-membrane protein, might be involved inconvergent extension in vertebrateembryos. In D. melanogaster, Stbm isknown to regulate the polarity of struc-tures in the insect cuticle (known as planarcell polarity) through the non-canonicalWnt signaling pathway2. In Xenopus laevis,overexpression of Stbm causes severelyshortened trunk structures, consistentwith a planar cell polarity or convergent-extension phenotype3,4. In the zebrafishDanio rerio, inhibition of Stbm activityleads to a reduction in anterior neuralmarkers, again suggesting that it has arole in mediating cell movements duringgastrulation5.

Jessen et al.1 now provide compellinggenetic evidence that Stbm regulatesconvergent extension in zebrafish. Theyshow by positional cloning that thezebrafish trilobite (tri) mutant (picturedhere), which has defects in gastrulationmovements and migration of hindbrainneurons, is allelic with Stbm. A series oftri alleles was found to have disruptionsof the Stbm coding region, and injection

of Stbm mRNA partially rescues triembryos. More impressive, Jessen et al.1

provide new insight into the precise roleof Stbm. By examining the length-to-width ratio of migratory ectodermalcells in wildtype and tri embryos, theyshow that the ratio is reduced in triembryos, as is the mediolateral align-ment of these cells. Moreover—andthere are time-lapse movies to provethis—the speed with which tri cellsmigrate to the dorsal midline isreduced. Finally, the authors show thathindbrain neurons in tri embryos can-not maintain the polarized orientationthat is a prerequisite for directed migra-tion. In other words, cells are aimlesswithout Stbm.

As noted in a recent review2, this grow-ing body of evidence suggests that the pla-nar cell polarity and convergent-extensionpathways are conserved in vertebrates, andin a range of animal phyla. Of special noteis the mouse ortholog of Strabismus,Ltap, which is mutated in the classicalneural tube mutant Loop-tail6. AlthoughLoop-tail has received a lot of attention asa model for spina bifida and other neuraltube anomalies in humans, Ltaphomozygotes have all of the other fea-tures of a convergent-extension pheno-type, including short anteroposterioraxes and wide notochords. �

—Alan Packer

1. Jessen, J.R. et al. Nature Cell Biol. 4 (2002); advanceonline publication, 8 July 2002(doi:10.1038/ncb828).

2. Wallingford, J.B., Fraser, S.E. & Harland, R.M. Dev.Cell 2, 695–706 (2002).

3. Darken, R.S. et al. EMBO J. 21, 976–985 (2002).4. Goto, T. & Keller, R. Dev. Biol. 247, 165–181 (2002).5. Park, M. & Moon, R.T. Nature Cell Biol. 4, 20–25

(2002).6. Kibar, Z. et al. Nature Genet. 28, 251–255 (2001).

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nature genetics • volume 31 • august 2002 335

Strabismus shows the wayEmbryonic cellular movements are dauntingly complex. A new study shows that anevolutionarily conserved pathway keeps cells pointed in the right direction.

Images courtesy of Jason Jessen (Vanderbilt University)

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