NEWS AND VIEWS site of class II MHC molecules is the CD4 and CDS, and whether they pro­ of a number of downstream homologous loop - residues 137-143 of vide the only sites of contact, are ques­ genes. the class II f3-chain - to that of class I tions awaiting the co crystallization of Unsuspected detail in the Drosophila which interacts with CDS. Konig et al.lO MHC molecules and their coreceptors. 0 response in vivo is becoming establish this point by muta~enesis of the apparent from the use of techniques, f3-chain; Cammarota et al. 1, in a com­ Peter Parham is in the Departments of such as immunocytology, with isoform­ plementary study, show that peptides Biology, and Microbiology and Im• specific antibodies for ecdysone recep­ derived from this region bind to CD4. munology, Stanford University School of tors (J. Truman, Univ. Washington, Exactly how these loops interact with Medicine, California 94305, USA. Seattle, with W. Talbot and D. Hog­ ness), or transcript analyses using finely staged material by both classical north­ GENE REGULATION -- ern analyses (F. Karim; C. Bayer, Univ. California, Berkeley) or simultaneous Ecdysone and the onion RTase-PCR analysis of isoforms of diffe­ rent primary response genes in tissues of Greg Guild and Geoff Richards individual Drosophila larvae (G.R.). These studies show that adjacent cells in THE axiom that more than half of the complexity proves insufficient to explain the same tissue may express different secret of finding something is knowing that response, there are further potential isoforms; that isoform switching where to look was well illustrated by two players in the receptor-related molecules in the primary response genes is a rapid, meetings* devoted to the molecular in Drosophila now under study (V. Hen­ but sometimes transient, response to analysis of steroid response in . rich, Univ. North Carolina, Greens­ ; and that there are clear differ­ By exploiting the combined genetic boro), and in the new primary respon­ ences in the regulation of the primary and in vivo approaches available with sive genes that have been isolated (P. response in different tissues of indi­ Drosophila, levels of detail in the steroid Hurban and A. Andres, Univ. Utah). viduals. Similar developmental studies in regulation of gene networks are emerg­ Comparative studies in other insects a number of tissues have revealed an ing that are rarely seen elsewhere. such as Manduca sexta (L. Riddiford, ecdysone response in the mid-third instar Although they are structurally related Univ. Washington, Seattle; W. Segraves, of Drosophila, which occurs before to vertebrate steroids, the ecdy­ Salk Inst.) and Galleria mellon ella (M. the dramatic hormone responses that sones seem to be harmless to Jindra, Caske Budovice, Czechoslova­ initiate pupariatioil and metamorphosis. even at their relatively high physiological kia) show that the D. melanogaster orga­ Molecular characterization of this re­ levels of 10-6 M. That stimulated many nization of these alternatively spliced sponse will be necessary to understand insect physiologists to characterize the genes is not unique. This bears on the the reprogramming of cells for the later steroid response with the aim of produc­ interpretation of certain novel isoforms ecdysone responses. Products of the ing ecdysone derivatives which might (for example one-fingered receptors)4 Broad Complex locus are also involved prove to be specific regulators of insect and opens the possibility of extending in many of the mid-third-instar responses populations. Their ingenuity in devising the results to insect species of medical or - but not all of them, as shown for the both in vivo and in vitro test systems economic importance. ecdysone-dependent modulation of the using ligatures, microsurgery and organ Every good needs a diptericin 's response to bacte­ culture has resulted in a detailed under­ DNA-binding site, and a clearer picture rial infection (M. Meister, Univ. Louis standing of the ecdysone response. But of the elusive EcRE (ecdysone response Pasteur), a first tentative link between the small size of insects proved to be a element) is now emerging. Although the endocrine and immune systems in liability in the biochemical isolation of closely related to the model hormone insects. the ecdysone receptors, and the molecu­ response elements of vertebrates, the For old hands all this showed that we lar breakthrough finally came from a insect elements are not necessarily de­ have penetrated another layer of the long-term Drosophila project. fined solely by consensus sequences (P. onion and, as best expressed by Jim Molecular analysis of the ecdysone and L. Cherbas, Indiana Univ.; C. Truman, we are in for a period of response in D. melanogaster was stimu­ Antoniewski and M. Laval, Inst. Jacques intense data collection before we can lated by the 'puffing' model Monod) and most probably require in­ hope to explain the remarkably rich of Ashburner et al. 1, and started with the teractions between receptors and other biological complexity, both in time and isolation of genes from defined puffs of transcription factors for their specific space, that characterizes the regulation the giant polytene . Fol­ activity in vivo. of these gene networks in vivo. It may lowing studies which revealed that three One striking feature of the meetings well be that the vertebrate laboratories, of the primary ecdysone responsive puffs was the return to the in vivo analysis of which have dominated the last decade of encode different families of transcription mutants, necessarily left to one side steroid research, will have something to 2 3 factors • , the ecdysone receptor itself during the difficult molecular analyses of learn from these studies. 0 has now been shown to be present in at the monster primary response genes least three isoforms (M. Koelle, W. whose isoform transcripts extend over Greg Guild is in the Department of Biolo• Talbot and D. Hogness, Stanford 100 kilobases. Particularly notable was gy, University of Pennsylvania, Phi• Univ.). The combinatorial possibilities the report of the rapid molecular charac­ ladelphia, Pennsylvania 19104-6018, of isoforms of both the receptor and the terization of strains bearing receptor USA. Geoff Richards is in the LGME du primary responsive genes are much lar­ mutants induced by classical mutagenesis CNRSIU184 de I'INSERMIInstitut de Chi• ger than those suggested by the formal (M. Bender and D. Hogness). Equally, mie Biologique, 67085 Strasbourg Cedex, model, and the present aim is to under­ mutants in two of the early genes, the France. stand the stage- and tissue-specific res­ Broad Complex (1. Deutsch, Inst. Jac­ ponse to a single hormonal stimulus ques Monod; G. G.; R. Hodgetts, Univ. 1. Ashburner, M. et al. Cold Spring Harb. Symp. quant. (ecdysone). If the available molecular Alberta; L. Von Kalm, Univ. California, Bioi. 38, 655-662 (1974). Berkeley; F. Karim, Univ. Utah) and 2. Thurnmel, C. S. BioEssays 12, 561-568 (1990). * Molecular Biology of Ecdysone Response Philadelphia. E74 (1. Fletcher, Univ. Utah) have been 3. Andres, A. & Thummel, C. S. Trends Genet. 8, 132-138 11 March. 1992. Tenth Ecdysone Workshop. University of (1992). Liverpool, 6-9 April, 1992. used to show their importance for the 4. Segraves, W. A. Cell 67, 225-228 (1991). NATURE· VOL357 . 18JUNE1992 539

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