The Drosophila svb/ovo gene gives rise to differentially expressed transcripts encoding a zinc finger protein. svb/ovo has two distinct genetic functions: shavenbaby (svb) is required for proper formation of extracellular projections that are produced by certain epidermal cells in late-stage differentiation; ovo is required for survival and differentiation of female germ cells. We cloned a mouse gene, movo1 encoding a nuclear transcription factor that is highly similar to its fly counterpart in its zinc-finger sequences. In mice, the gene is expressed in skin, where it localizes to the differentiating cells of epidermis and hair follicles, and in testes, where it is present in spermatocytes and spermatids. Using gene targeting, we show that movo1 is required for proper development of both hair and sperm. movo1 −/− mice are small, produce aberrant hairs, and display hypogenitalism, with a reduced ability to reproduce. These mice also develop abnormalities in kidney, where movo1 is also expressed. Our findings reveal remarkable parallels between mice and flies in epidermal appendage formation and in germ-cell maturation. Furthermore, they uncover a phenotype similar to that of Bardet-Biedl syndrome, a human disorder that maps to the same locus as human ovo1.

Sequence comparisons of vitellogenins from a wide range oforganisms have identified regions of similarity not only to each other but also to vertebrate apolipoproteins (e.g. apoB-100 and apoE). Furthermore, the chicken vitellogenin receptor, which also binds apolipoproteins, has been found to belong to the low density lipoprotein receptor (LDLR) superfamily [Bujo, H., Hermann, M., Kaderli, M. O., Jacobsen, L., Sugawara, S., Nimpf, J., Yamamoto, T. & Schneider, W. J. (1994) EMBO J. 13,[5165][5166][5167][5168][5169][5170][5171][5172][5173][5174][5175]. The yolk proteins of higher dipterans are exceptional, however, and instead show similarity to lipoprotein lipases. The molecular characterization of the putative Drosophila melknogaster vitellogenin receptor gene, yolkless (yl), described in this report reveals that the protein it encodes (Yl), is also a member of the LDLR superfamily. The ovary-specific 6.5-kbyl RNA codes for a protein of -210 kDa which contains all three motifs common to the LDLR class of proteins. Within this superfamily, Yl may be related more to the LDLR-related proteins (LRPs), which bind both apolipoproteins and lipoprotein lipases. The similarity of Y1 to the other LDLR proteins is restricted to the putative extracellular domain. Most noticeably, the cytoplasmic domain of Yl lacks the typical NPXY sequence which is involved in receptor internalization.One of the best-studied mechanisms for the selective uptake of proteins into cells is receptor-mediated endocytosis. Two key advances in the study of endocytosis have been the development of cell-free assays and the identification of mutations which disrupt specific steps of endocytosis (1, 2). In this regard, we have been interested in identifying mutations which affect endocytosis in Drosophila. We have focused on the uptake of vitellogenins (yolk proteins) into the developing egg for several reasons. First, oocytes incorporate large amounts of vitellogenins (3, 4). Second, in oocytes, a specialized mechanism has evolved so that the yolk proteins are stored in yolk granules instead of being fated for degradation in lysosomes. Third, in many insects, juvenile hormone is required for the oocyte to initiate vitellogenin uptake (4, 5).Obviously, one of the key components in the uptake of vitellogenins is the receptor, and although vitellogenins from a variety of organisms have been characterized, much less is known about their receptors. In vertebrates, one of the beststudied systems is the chicken oocyte 95-kDa receptor, which binds two components of chicken yolk-vitellogenin and very low density lipoproteins (6). Mutants lacking this receptor fail to accumulate yolk proteins in the oocyte, and plasma vitellogenin levels are elevated (6, 7). Recently, Bujo et al. (8) have shown that the 95-kDa receptor is closely related to the mammalian very low density lipoprotein receptor (VLDLR). Frog and fish vitellogenin receptors appear to be related to the chicken receptor (9, 10).By using ligand-binding assays, vitellogenin receptors of simil...

In many insects, development of the oocyte arrests temporarily just before vitellogenesis, the period when vitellogenins (yolk proteins) accumulate in the oocyte. Following hormonal and environmental cues, development of the oocyte resumes, and endocytosis of vitellogenins begins. An essential component of yolk uptake is the vitellogenin receptor. In this report, we describe the ovarian expression pattern and subcellular localization of the mRNA and protein encoded by the Drosophila melanogaster vitellogenin receptor gene yolkless (yl). yl RNA and protein are both expressed very early during the development of the oocyte, long before vitellogenesis begins. RNA in situ hybridization and lacZ reporter analyses show that yl RNA is synthesized by the germ line nurse cells and then transported to the oocyte. Yl protein is evenly distributed throughout the oocyte during the previtellogenic stages of oogenesis, demonstrating that the failure to take up yolk in these early stage oocyte is not due to the absence of the receptor. The transition to the vitellogenic stages is marked by the accumulation of yolk via clathrin-coated vesicles. After this transition, yolk protein receptor levels increase markedly at the cortex of the egg. Consistent with its role in yolk uptake, immunogold labeling of the receptor reveals Yl in endocytic structures at the cortex of wild-type vitellogenic oocytes. In addition, shortly after the inception of yolk uptake, we find multivesicular bodies where the yolk and receptor are distinctly partitioned. By the end of vitellogenesis, the receptor localizes predominantly to the cortex of the oocyte. However, during oogenesis in yl mutants that express full-length protein yet fail to incorporate yolk proteins, the receptor remains evenly distributed throughout the oocyte. INTRODUCTIONThe magnitude of yolk uptake into the oocyte during vitellogenesis suggests a heavy involvement of the endocytic machinery; indeed, the clathrin-coated vesicle was originally described in the vitellogenic mosquito oocyte (Roth and Porter, 1964). Because the morphological features are so striking, descriptions of vitellogenesis have been made in a broad range of oviparous species, including birds (Perry and Gilbert, 1979;Perry et al., 1984), frogs (Opresko and Wiley, 1987;Wall and Patel, 1987), fish (reviewed by Wallace andSelman, 1990), and insects (Cummings andMahowald, 1972; Giorgi and Jacob, 1977a,b;Raikhel, 1984;van Antwerpen et al., 1993) (reviewed by Raikhel and Dhadialla, 1992). In several cases, immunocytochemical and ultrastructural studies using labeled yolk protein precursors or fluid phase markers have followed the fate of the proteins as they are sorted to the yolk platelets (Giorgi and Jacob, 1977a;Raikhel, 1984;Busson et al., 1989). The initial steps in the yolk uptake pathway are similar to those described for general receptor-mediated endocytosis (Goldstein et al., 1985;Mukherjee et al., 1997). Vitellogenins (Vgs) are taken up through clathrin-coated pits, and they accumulate initially in vesiculotubul...

Drosophila ovo͞svb (dovo) is required for epidermal cuticle͞den-ticle differentiation and is genetically downstream of the wg signaling pathway. Similarly, a mouse homolog of dovo, movo1, is required for the proper formation of hair, a mammalian epidermal appendage. Here, we provide biochemical evidence that movo1 encodes a nuclear DNA binding protein (mOvo1a) that binds to DNA sequences similar to those that dOvo binds to, further supporting the notion that mOvo1a and dOvo are genetically and biochemically homologous proteins. Additionally, we show that the movo1 promoter is activated by the lymphoid enhancer factor 1 (LEF1)͞␤-catenin complex, a transducer of wnt signaling. Collectively, our findings suggest that movo1 is a developmental target of wnt signaling during hair morphogenesis in mice, and that the wg͞wnt-ovo link in epidermal appendage regulatory pathways has been conserved between mice and flies.hair follicle ͉ wnt ͉ wg ͉ mouse ovo1

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We have discovered a novel DNA sequence element in Drosophila which is based upon a CTGA tandem repeat. This element has been named the YYRR box to emphasize its dipyrimidine-dipurine nature which is predicted to have unusual structural features. Southern hybridization analysis of genomic DNA indicates the presence of 25-30 copies of the YYRR box in each of three Drosophila species (melanogaster, pseudoobscura, and virilis) and conservation of genomic location within species. Similar analysis of human and rat DNA indicates the presence of YYRR related sequences in mammals as well. YYRR boxes have been localized to two genetic loci in Drosophila: Gld and a gene tentative identified as ted. These two genes exhibit correlated patterns of developmental expression and an identical mutant phenotype. Sequence analysis of the Gld YYRR box in three Drosophila species revealed a high degree of conservation despite its intronic location.

The Gld gene of Drosophila melanogaster is transiently expressed during every stage of development. The temporal pattern of Gld expression is highly correlated with that of ecdysteroids. Exogeneous treatment of third instar larvae with 20-hydroxyecdysone induces the accumulation of Gld mRNA in the hypoderm and anterior spiracular gland cells. During metamorphosis Gld is expressed in a variety of tissues derived from the ectoderm. In the developing reproductive tract, Gld mRNA accumulates in the female spermathecae and oviduct and in the male ejaculatory duct and ejaculatory bulb. These four organs are derived from closely related cell lineages in the genital imaginal disc. Since the expression of Gld is not required for the development of these reproductive structures, this spatial pattern of expression is most likely a fortuitous consequence of a shared regulatory factor in this cell lineage. At the adult stage a high level of the Gld mRNA is only observed in the male ejaculatory duct.