The Nonsense Police a Head with No Torso

HIGHLIGHTS

EVO-DEVO A head with no torso

When we think of Drosophila,it’s often wild-type Bicoid protein suffice to res- in terms of the genes and processes cue the anterior defects of terminal- that it has in common with higher ani- pathway mutants. This argues that mals. The well scrutinized pathway of one function of Tor is to potentiate how a fly embryo tells its head from its the anterior system, as the rescue tail (and everything inbetween) has occurs by upregulating downstream laid the paradigm for the patterning targets, such as huckebein. GENE EXPRESSION function of morphogens in develop- The additive effect of the terminal ment. But it is puzzling that many system on bcd had already been sus- other insects — never mind ourselves pected: hypomorphic mutants of bcd, The nonsense police — don’t undergo patterning in quite or mutations in the genes that localize the same way. The fly uses two differ- bcd mRNA, look virtually identical to RNA transcripts that encode truncated proteins are ent pathways to specify the anterior tip embryos with terminal phenotypes, eliminated from eukaryotic cells by a process known as of its head. Now Schaeffer et al.show with double mutants being much more mRNA surveillance. In yeast and Caenorhabditis elegans, that these two pathways, whose func- severe. In addition, correct huckebein classical genetic approaches have identified some of the genes tion in anterior development has been expression can be induced by either Tor required for this surveillance. A puzzle, however, is why acquired recently in evolution, con- or Bcd activity alone. mRNA surveillance exists at all. What are the natural targets? verge on similar targets and that Bicoid seems to be a recently Mitrovich and Anderson provide some possible answers. removal of one of them can be com- acquired gene in fruitflies, and the use The authors reasoned that, in a C. elegans mRNA pensated by boosting the other. of bcd and tor at the anterior is an surveillance mutant (smg-2), RNA transcripts that are The Drosophila body plan is set up eccentricity of Drosophila. targets for mRNA surveillance will tend to be present at by the action of three sets of maternally If, as is proposed, Tor antagonises higher levels, relative to wild-type strains. This was the contributed genes: the anterior, poste- repressors of Bcd targets then, in insects basis for an RNA subtraction experiment and, sure enough, rior and terminal systems. The termi- that lack bcd, the anterior terminal sys- transcripts were identified that were enriched in the nal system requires local signalling tem could assist other genes (e.g. ortho- surveillance mutant. through the Torso (Tor) receptor tyro- denticle, thought to be one of the Gene transcripts for four ribosomal proteins were sine kinase, which specifies the extreme ancestral head determinants). The fact repeatedly represented in the selected pool and, in all cases, tips of the head and tail. The anterior that tor is dispensable for head develop- the transcript was aberrant, containing part of an intron and posterior systems consist of local- ment might explain why most insects that would normally have been removed by splicing. The ized mRNAs that, once translated, (e.g. with short germband develop- intronic sequence also contained in-frame stop codons. form gradients that regulate target ment) can form a head even if it devel- Overall, it seems that these ribosomal protein genes genes in a concentration-dependent ops further down the egg. produce two types of transcript — a productive and an manner. The homeoprotein Bicoid is Tanita Casci aberrant transcript — and the aberrant transcript is the most notable among the anterior- – normally removed by mRNA surveillance. group genes, and embryos born to bcd References and Links Mitrovich and Anderson found that the intronic mothers lack a head, thorax and part of ORIGINAL RESEARCH PAPER Schaeffer, V. et al. sequences present in the aberrant transcripts are highly the abdomen. High Bicoid levels render the terminal system dispensable for Drosophila head development. conserved among a group of nematodes, suggesting that Schaeffer et al. show that, in the Development 127, 3993–3999 (2000). the sequences have functional significance, despite not anterior of the fly embryo, bcd and tor REVIEW Dearden, P. et al. Developmental evolution: encoding protein. The authors speculate that this function are part of two independent pathways Axial patterning in insects. Curr. Biol. 9, R591–R594 (1999). helps to ensure the tight regulation of ribosomal protein that share common target genes. FURTHER READING Wimmer, E. A. et al. bicoid- levels. When ribosomal protein levels rise, one way of What’s more, a deletion mutant of bcd independent formation of thoracic segments in reducing new protein synthesis is to bias splicing towards that is expressed 3–4 times higher Drosophila. Science 287, 2476–2479 (2000). | Schröder, R. et al. Conserved and divergent aspects the aberrant transcripts, and the authors provide data than the wild-type protein can rescue of terminal patterning in the beetle Tribolium to support this view. But then the cell has a problem — the phenotype of the tor pathway, to castaneum. Proc. Natl Acad. Sci. USA 97, 6591–6596 (2000). the aberrant transcript could encode a truncated, and give embryos with normal anterior LAB PAGES Claude Desplan’s lab page at NYU possibly deleterious, protein. At that point, the structures. Indeed, increased doses of WEB SITES Flybase, the Drosophila database surveillance mechanism steps in and removes the offending transcripts. Mark Patterson

References and links ORIGINAL RESEARCH PAPER Mitrovich, Q. M. & Anderson, P. Unproductively spliced ribosomal protein mRNAs are natural targets of mRNA surveillance in C. elegans. Genes Dev. 14, 2173–2184 (2000). FURTHER READING Hilleren, P. & Parker, R. Mechanisms of mRNA surveillance in Bicoid protein is expressed at the anterior of the embryo (left), where it reinforces eukaryotes. Annu. Rev. Genet. 33, 229–260 (1999). the expression of crocodile, a target of the Torso terminal pathway (right). WEB SITES Phil Anderson’s homepage Courtesy of Valérie Schaeffer and Ernst Wimmer.