MONITOR

A ‘digest’ of some recent papers of interest in the primary journals

MEETING REPORTS

TIG MAY 1998 VOL. 14 NO. 5

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reported the use of conjugationalequipment for takeover of host im-mune cells by intracellular bacterialpathogens6. Transcriptional anti-termination, once a peculiarity ofphage l gene regulation, was de-scribed in B. subtilis, which uses thesame strategy but a different mecha-nism from l (Tina Henkin, OhioState Univ., USA).

Much other exciting work waspresented in the areas of replicational,

transcriptional and translational regu-lation, DNA rearrangement, and otherbasic, conserved mechanisms bywhich DNA makes its living anddirects cells to make theirs.

Susan M. Rosenbergsmr@bcm.tmc.edu

Department of Molecular and Human Genetics,Baylor College of Medicine, One Baylor Plaza,

Houston, TX 77030-3498, USA.

Further reading1 Bramhill, D. (1997) Annu. Rev. Cell

Dev. Biol. 13, 395–4242 http://golgi.harvard.edu/losick/

movies3 Kogoma, T. (1997) Microbiol. Mol.

Biol. Rev. 61, 212–2384 Rosenberg, S.M. (1997) Curr. Opin.

Genet. Dev. 7, 829–8345 Perler, F.B. (1998) Cell 92, 1–46 Vogel, J.P. et al. (1998) Science 279,

873–876Supported by NIH (USA) grant R01GM53158.

EPH receptor tyrosine kinases are keyplayers in vertebrate axon guidance andcell migration, controlling chemorepul-sive responses of cells to cell-associatedligands. This is the first example of anEPH receptor in Caenorhabditis elegans,encoded by the vab-1 gene. Mutationsof vab-1 affect both the closure of ventralclefts and the ventral enclosure by theepidermis. Neuroblasts and epidermalcells differentiate correctly but are dis-turbed in their patterns of movement,leading to aberrant morphogenesis.Interestingly, the vab-1 gene is expressed

in ventral neuroblasts rather than theepidermal cells, suggesting a non-autonomous influence over epidermalmorphogenesis. Additionally, weakphenotypes are still produced by recep-tors predicted to be kinase-defective;therefore kinase-independent functionsmight be involved. So now we haveexamples of apparent ‘reverse’ signallingby these enzymes both in vertebrates(EPHB2) and in invertebrates (VAB-1).What can VAB-1 tell us about epidermalmorphogenesis and EPH receptor func-tion? The authors propose two possible

roles for the VAB-1 enzyme. First, it mightgovern the movement of neuroblasts,which are in turn used as a ‘substrate’for epidermal cell migration. Second,VAB-1 might signal directly to migratingepidermal cells, perhaps even in a repul-sive fashion. Further insight dependscritically on the identification and localiz-ation of the ligand(s) for VAB-1. EPHreceptors have now been implicated ingrowth cone motility, neural crest motil-ity, and neuroblast and epidermal mor-phogenesis. As the authors remark, EPHreceptor function in epithelial morpho-genesis might now be confirmed inmammals, given that mice lacking thereceptors EPHB2 and EPHB3 have cleftpalates, and other family members areexpressed in tissues, such as lung, thatundergo intense epithelial morpho-genesis during development. ✍

C. elegans EPH receptor

The VAB-1 EPH receptor tyrosine kinase functions in neural and epithelial morphogenesis in C. elegans.

George, S.E., Simokat, K., Hardin, J. and Chisholm, A. Cell 92, 633–643

Sox genes encode a large family of pro-teins that have tissue-specific patterns ofexpression. Sox genes appear to functionboth as classical transcription factors andas organizers of local chromatin structure.Recently, one family member, SOX10,has been proposed as a strong candidatefor the Waardenburg–Shah (WS4) andthe Hirschsprung (HSCR) syndromes.WS4 and HSCR are both characterized ascongenital disorders caused by defectsin embryonic neural crest cells. In mice,

several models for HSCR exist, includingthe dom mutation. Mice heterozygous fordom have defects in neural-crest-derivedenteric ganglia, while homozygous ani-mals die in utero. Southard-Smith et al.use linkage analysis to map the dommutation to a 0.1 cM region containingSox10. In dom mice, a single nucleo-tide insertion exists in the Sox10 codingregion, and Sox10 is expressed in celltypes effected by the dom mutation.Human HSCR is mainly associated with

mutations in RET, a kinase receptor, butsome patients with HSCR have mu-tations in a number of other genes,including EDN3, EDNRB and GDNF.Pingault et al. show that patients suffer-ing from WS4 (a disease similar to HSCRbut with the additional complications ofdeafness and pigmentary defects) isassociated with mutations in the SOX10gene. Although hearing loss has not beenreported for the dom mice, the pheno-type of these mice is strain-dependent,suggesting that in certain genetic back-grounds other defects associated withWS4 might arise, and thus dom might bea model for WS4 rather than HSCR. Be-cause some defects are strain-dependent,it is possible that strain-specific modi-fiers will be identified that might aid inthe characterization of phenotypic deter-minants of the human disease. ✍

Odd SOX

Sox10 mutation disrupts neural crest development in Dom Hirschsprung mouse modelSouthard-Smith, E.M., Kos, L. and Pavan, W.J. Nat. Genet. 18, 60–64

SOX10 mutation in patients with Waardenburg–Hirschsprung diseasePingault, V. et al. Nat. Genet. 18, 171–173