Search

Studies of Drosophila metamorphosis have been hampered by our inability to visualize many of the remarkable changes that occur within the puparium. To circumvent this problem, we have expressed GFP in specific tissues of living prepupae and pupae and compiled images of these animals into time-lapse movies. These studies reveal, for the first time, the dynamics and coordination of morphogenetic movements that could only be inferred from earlier studies of dissected staged animals. We also identify responses that have not been described previously. These include an unexpected variation in some wild-type animals, where one of the first pairs of legs elongates in the wrong position relative to the second pair of legs and then relocates to its appropriate location. At later stages, the antennal imaginal discs migrate from a lateral position in the head to their final location at the anterior end, as leg and mouth structures are refined and the wings begin to fold. The larval salivary glands translocate toward the dorsal aspect of the animal and undergo massive cell death following head eversion, in synchrony with death of the abdominal muscles. These death responses fail to occur in [rbp.sup.5] mutants of the Broad-Complex (BR-C), and imaginal disc elongation and eversion is abolished in [br.sup.5] mutants of the BR-C. Leg malformations associated with the [crol.sup.3] mutation can be seen to arise from defects in imaginal disc morphogenesis during prepupal stages. This approach provides a new tool for characterizing the dynamic morphological changes that occur during metamorphosis in both wild-type and mutant animals. Keywords: Ecdysone; Imaginat discs; Larval muscles; Morphogenesis; Cell death; Adult development

Drosophila imaginal discs are specified and patterned during embryonic and larval development, resulting in each cell acquiring a specific fate in the adult fly. Morphogenesis and differentiation of imaginal tissues, however, does not occur until metamorphosis, when pulses of the steroid hormone ecdysone direct these complex morphogenetic responses. In this paper, we focus on the role of ecdysone in regulating adult wing development during metamorphosis. We show that mutations in the EcR ecdysone receptor gene and crooked legs (crol), an ecdysone-inducible gene that encodes a family of zinc finger proteins, cause similar defects in wing morphogenesis and cell adhesion, indicating a role for ecdysone in these morphogenetic responses. We also show that crol and EcR mutations interact with mutations in genes encoding integrin subunits--a family of [Alpha][Beta] heterodimeric cell surface receptors that mediate cell adhesion in many organisms, [Alpha]-Integrin transcription is regulated by ecdysone in cultured larval organs and some changes in the temporal patterns of integrin expression correlate with the ecdysone titer profile during metamorphosis. Transcription of [Alpha]- and [Beta]-integrin subunits is also altered in crol and EcR mutants, indicating that integrin expression is dependent upon crol and EcR function. Finally, we describe a new hypomorphic mutation in EcR which indicates that different EcR isoforms can direct the development of adult appendages. This study provides evidence that ecdysone controls wing morphogenesis and cell adhesion by regulating integrin expression during metamorphosis. We also propose that ecdysone modulation of integrin expression might be widely used to control multiple aspects of adult development, [C] 2000 Academic Press Key Words: metamorphosis; ecdysone; nuclear receptor; transcription; morphogenesis; cell adhesion; integrins.

The chromosomal passenger complex (CPC), composed of a kinase component, Aurora B, the scaffolding subunit inner centromeric protein, Borealin, and Survivin, is a key regulator of cell division. It controls multiple events, from chromosome condensation in prophase to the final separation or abscission of the two daughter cells. The essential functions of the CPC during metaphase, however, have always hindered an accurate study of its role during cytokinesis. The recent development of small molecule inhibitors against Aurora B and the use of elegant technologies such as chemical genetics have offered new approaches to study the functions of the CPC at the end of cell division. Here, we review the recent findings about the roles of the CPC in controlling the assembly of the cleavage furrow, central spindle, and midbody. We will also discuss the crucial function of this complex in controlling abscission timing in order to prevent abscission when lagging chromatin is present at the cleavage site, thereby avoiding the formation of genetically abnormal daughter cells. Finally, we offer our perspective on how to exploit the potential therapeutic applications of inhibiting CPC activity during cytokinesis in cancer cells. [ABSTRACT FROM AUTHOR]

The meiotic generation of haploid gametes with equal contents of genetic material is important for sexual reproduction in mammals. Errors in the transmission of chromosomes during meiosis may lead to aneuploidy, which is the leading cause of miscarriage and congenital birth defects in humans. The Aurora kinases, which include Aurora- A, Aurora-B, and Aurora-C, are highly conserved serine-threonine kinases that play essential roles in centrosome function, chromosome segregation, and cytokinesis during mitosis and meiosis. While Aurora-A and Aurora-B have been extensively studied in mitosis, the role of Aurora-C in meiosis is only now starting to be revealed. For example, the perturbation of Aurora-C kinase activity by microinjection of Aurora-C-kinase-dead mutant mRNAs into mouse oocytes induced multiple defects, including chromosome misalignment, abnormal kinetochore-microtubule attachment, premature chromosome segregation, and failure of cytokinesis during meiotic division. However, the analysis of such defects is complicated by the possibility that Aurora-B may be present in mammalian germ cells. Interestingly, a homozygous mutation of Aurora-C in humans leads to the production of large-headed polyploid spermatozoa and causes male infertility, but homozygous females are fertile. Mouse studies regarding the roles of Aurora-B and Aurora-C in female meiotic divisions have yielded inconsistent results, and it has proven difficult to explain why homozygous human females have no significant clinical phenotype. In this review, we will discuss the controversial status of Aurora-B in oocytes and the possible role of Aurora-C during meiotic division. [ABSTRACT FROM AUTHOR]