The Drosophila eye is a polarized epithelium in which ommatidia of opposing chirality fall on opposite sides of the eye's midline, the equator. The equator is established in at least two steps: photoreceptors R3 and R4 adopt their fates, and then ommatidia rotate clockwise or counterclockwise in accordance with the identity of these photoreceptors. We report the role of two cadherins, Fat (Ft) and Dachsous (Ds), in conveying the polarizing signal from the D/V midline in the Drosophila eye. In eyes lacking Ft, the midline is abolished. In ft and ds mutant clones, wild-type tissue rescues genetically mutant tissue at the clonal borders, giving rise to ectopic equators. These ectopic equators distort a mosaic analysis of these genes and led to the possible misinterpretation that ft and ds are required to specify the R3 and R4 cell fates, respectively. Our interpretation of these data supports a significantly different model in which ft and ds are not necessarily required for fate determination. Rather, they are involved in long-range signaling during the formation of the equator, as defined by the presence of an organized arrangement of dorsal and ventral chiral ommatidial forms.

Shwachman-Diamond Syndrome (SDS) is a rare multisystem disorder characterized by exocrine pancreatic insuffi-ciency, bone marrow dysfunction, and metaphyseal chondrodysplasia. Recent studies show that mutations of SBDS, a gene of unknown function, are present in the majority of patients with SDS. In the present study, we show that most, but not all, patients classified based on rigorous clinical criteria as having SDS had compound heterozygous mutations of SBDS. Full-length SBDS protein was not detected in leukocytes of SDS patients with the most common SBDS mutations, consistent with a loss-of-function mechanism. In contrast, SBDS protein was expressed at normal levels in SDS patients without SBDS mutations. These data confirm the absence of SBDS mutations in this subgroup of patients and suggest that SDS is a genetically heterogeneous disorder. The presence (or absence) of SBDS mutations may define subgroups of patients with SDS who share distinct clinical features or natural history. (Blood. 2004;104: 3588-3590) Introduction Shwachman-Diamond Syndrome (SDS) is a rare multisystem disorder characterized by exocrine pancreatic insufficiency, bone marrow dysfunction, and metaphyseal chondrodyspla-sia. 1-5 SDS is the second most common cause of congenital exocrine pancreatic insufficiency, after cystic fibrosis. Bone marrow dysfunction is present in nearly all patients with SDS. 3-6 In the largest published series (88 patients), chronic or intermittent neutropenia was present in 97%. 5 Anemia and thrombocyto-penia were present in more than a third of patients. Patients with SDS have a marked propensity to develop myelodysplasia or acute myeloid leukemia. 6-8 SDS is inherited in an autosomal recessive fashion. 9 Recently , Boocock et al 10 reported that compound heterozygous mutations of the SBDS (Shwachman-Bodian-Diamond syndrome) gene on chromosome 7 were present in the majority of patients with SDS. Most of these mutations resulted from gene conversion with a neighboring pseudogene (SBDSP). Similar data were reported in a smaller series of patients of Japanese ancestry. 11 Most of the SBDS mutations are predicted to truncate a substantial portion of the SBDS protein, suggesting that they act in a loss-of-function manner. Herein, we show that most, but not all, patients classified prospectively based on clinical criteria as having probable SDS had SBDS gene mutations. Moreover, a strong correlation between SBDS genotype and expression of full-length SBDS protein was observed. Study design Human subjects There were 33 families who attended the Second International Conference on Shwachman-Diamond Syndrome in St Louis in 1999 and who were invited to participate in a study to elucidate the genetic basis of SDS. After obtaining informed consent, a thorough history, physical examination, review of medical records, and selected laboratory testing were performed. In addition, genomic DNA was extracted from peripheral blood leukocytes using standard protocols. The diagnosis of SDS was based on the presence of the followin...

Tissue polarity in Drosophila is regulated by a number of genes that are thought to function in a complex, many of which interact genetically and/or physically, co-localize, and require other tissue polarity proteins for their localization. We report the enhancement of the strabismus tissue polarity phenotype by mutations in two other tissue polarity genes, flamingo and prickle. Flamingo is autonomously required for the establishment of ommatidial polarity. Its localization is dynamic throughout ommatidial development and is dependent on Frizzled and Notch. Flamingo and Strabismus co-localize for several rows posterior to the morphogenetic furrow and subsequently diverge. While neither of these proteins is required for the other's localization, Prickle localization is influenced by Strabismus function. Our data suggest that Strabismus, Flamingo and Prickle function together to regulate the establishment of tissue polarity in the Drosophila eye.

Shwachman-Diamond syndrome (SDS) is

The tissue polarity pathway is required for the establishment of epithelial polarity in a variety of vertebrate and invertebrate organs. Core tissue polarity proteins act in a dynamically regulated complex to direct the polarization of the Drosophila eye. We report the identification and characterization of bedraggled (bdg), a novel gene that regulates one output of the tissue polarity pathway-the establishment of the R3/R4 photoreceptor fates. bdg encodes a novel, putative transporter protein and interacts genetically with all of the core polarity genes to influence the specification of the R3 and R4 cell fates. Finally, bdg is required for both viability and the initial stages of imaginal disc development.