Isolation and characterisation of murine homologues of the Drosophila seven in absentia gene (sina)

Development ◽  
1993 ◽  
Vol 117 (4) ◽  
pp. 1333-1343
Author(s):  
N.G. Della ◽  
P.V. Senior ◽  
D.D. Bowtell

The seven in absentia gene (sina) is required for formation of the R7 photoreceptor cell in the developing eye of Drosophila melanogaster. The sina protein contains a putative zinc finger domain and localises to the cell nucleus in Drosophila. We report here the identification of a family of genes in the mouse (designated Siah) with extensive sequence homology to Drosophila sina. The Siah genes fall into two main groups: Siah-1, which consists of four closely related members, two of which appear to be functional, and Siah-2, which contains a single functional member. The predicted Siah proteins show an unusually high degree of conservation with sina over the majority of their lengths, diverging significantly only at their amino terminal ends. The Siah-1 and Siah-2 genes are widely expressed at a low level in the embryo and adult. Analysis of Siah-2 by hybridisation histochemistry shows that it is expressed at a higher level in a restricted number of sites during development, including the olfactory epithelium, retina, forebrain and proliferating cartilage of developing bone. The striking degree of sequence homology observed between the Drosophila and murine genes implies strong conservation pressure on the Siah genes and suggests that they play a significant role in vertebrate development.

1994 ◽  
Vol 269 (7) ◽  
pp. 5288-5296
Author(s):  
R.C. Hapak ◽  
H. Zhao ◽  
J.M. Boschi ◽  
M.T. Henzl

Genetics ◽  
1996 ◽  
Vol 144 (2) ◽  
pp. 635-645 ◽  
Author(s):  
David A Kirby ◽  
Wolfgang Stephan

Abstract We surveyed sequence variation and divergence for the entire 5972-bp transcriptional unit of the white gene in 15 lines of Drosophila melanogaster and one line of D. simulans. We found a very high degree of haplotypic structuring for the polymorphisms in the 3′ half of the gene, as opposed to the polymorphisms in the 5′ half. To determine the evolutionary mechanisms responsible for this pattern, we sequenced a 1612-bp segment of the white gene from an additional 33 lines of D. melanogaster from a European and a North American population. This 1612-bp segment encompasses an 834bp region of the white gene in which the polymorphisms form high frequency haplotypes that cannot be explained by a neutral equilibrium model of molecular evolution. The small number of recombinants in the 834bp region suggests epistatic selection as the cause of the haplotypic structuring, while an investigation of nucleotide diversity supports a directional selection hypothesis. A multi-locus selection model that combines features from both-hypotheses and takes the recent history of D. melanogaster into account may be the best explanation for these data.


1986 ◽  
Vol 6 (2) ◽  
pp. 626-634 ◽  
Author(s):  
G S Adrian ◽  
M T McCammon ◽  
D L Montgomery ◽  
M G Douglas

The ADP/ATP translocator, a transmembrane protein of the mitochondrial inner membrane, is coded in Saccharomyces cerevisiae by the nuclear gene PET9. DNA sequence analysis of the PET9 gene showed that it encoded a protein of 309 amino acids which exhibited a high degree of homology with mitochondrial translocator proteins from other sources. This mitochondrial precursor, in contrast to many others, does not contain a transient presequence which has been shown to direct the posttranslational localization of proteins in the organelle. Gene fusions between the PET9 gene and the gene encoding beta-galactosidase (lacZ) were constructed to define the location of sequences necessary for the mitochondrial delivery of the ADP/ATP translocator protein in vivo. These studies reveal that the information to target the hybrid molecule to the mitochondria is present within the first 115 residues of the protein. In addition, these studies suggest that the "import information" of the amino-terminal region of the ADP/ATP translocator precursor is twofold. In addition to providing targeting function of the precursor to the organelle, these amino-terminal sequences act to prevent membrane-anchoring sequences located between residues 78 and 98 from stopping import at the outer mitochondrial membrane. These results are discussed in light of the function of distinct protein elements at the amino terminus of mitochondrially destined precursors in both organelle delivery and correct membrane localization.


2002 ◽  
Vol 22 (11) ◽  
pp. 3685-3697 ◽  
Author(s):  
Kai Ping Sem ◽  
Baharak Zahedi ◽  
Ivan Tan ◽  
Maria Deak ◽  
Louis Lim ◽  
...  

ABSTRACT We have characterized Drosophila melanogaster ACK (DACK), one of two members of the ACK family of nonreceptor tyrosine kinases in Drosophila. The ACKs are likely effectors for the small GTPase Cdc42, but signaling by these proteins remains poorly defined. ACK family tyrosine kinase activity functions downstream of Drosophila Cdc42 during dorsal closure of the embryo, as overexpression of DACK can rescue the dorsal closure defects caused by dominant-negative Dcdc42. Similar to known participants in dorsal closure, DACK is enriched in the leading edge cells of the advancing epidermis, but it does not signal through activation of the Jun amino-terminal kinase cascade operating in these cells. Transcription of DACK is responsive to changes in Dcdc42 signaling specifically at the leading edge and in the amnioserosa, two tissues involved in dorsal closure. Unlike other members of the ACK family, DACK does not contain a conserved Cdc42-binding motif, and transcriptional regulation may be one route by which Dcdc42 can affect DACK function. Expression of wild-type and kinase-dead DACK transgenes in embryos, and in the developing wing and eye, reveals that ACK family tyrosine kinase activity is involved in a range of developmental events similar to that of Dcdc42.


1993 ◽  
Vol 13 (10) ◽  
pp. 6558-6571 ◽  
Author(s):  
G Bolger ◽  
T Michaeli ◽  
T Martins ◽  
T St John ◽  
B Steiner ◽  
...  

We have isolated cDNAs for four human genes (DPDE1 through DPDE4) closely related to the dnc learning and memory locus of Drosophila melanogaster. The deduced amino acid sequences of the Drosophila and human proteins have considerable homology, extending beyond the putative catalytic region to include two novel, highly conserved, upstream conserved regions (UCR1 and UCR2). The upstream conserved regions are located in the amino-terminal regions of the proteins and appear to be unique to these genes. Polymerase chain reaction analysis suggested that these genes encoded the only homologs of dnc in the human genome. Three of the four genes were expressed in Saccharomyces cerevisiae and shown to encode cyclic AMP-specific phosphodiesterases. The products of the expressed genes displayed the pattern of sensitivity to inhibitors expected for members of the type IV, cyclic AMP-specific class of phosphodiesterases. Each of the four genes demonstrated a distinctive pattern of expression in RNA from human cell lines.


Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1979-1979 ◽  
Author(s):  
Belinda K Singleton ◽  
David Roxby ◽  
John Stirling ◽  
Frances A Spring ◽  
Carolyn Wilson ◽  
...  

Abstract Abstract 1979 Poster Board I-1001 The X-borne transcription factor GATA-1 is essential for erythroid and megakaryocyte development. In 1986, Norman et al. (Vox Sang 51:49) described a large family in which the rare Lu(a-b-) blood group phenotype is inherited as the result of an X-borne gene. Serologic and flow cytometric analyses confirmed the suppression of Lutheran blood group antigens on the red blood cells from the original male propositus. Analysis of DNA from the propositus revealed a mutation (1240T>C) in the termination codon of GATA1 converting TGA to a codon for arginine (CGA). The mutation predicts a translated GATA-1 protein containing an additional 41 amino acids at the carboxy terminus. DNA from an unaffected sister of the propositus had a wild-type GATA1 sequence. The GATA1 mutation was not present in 78 random blood donors as determined by restriction fragment length polymorphism (RFLP) analysis using BspHI. The propositus, who is now 64, has an Hb of 122 g/l, a low platelet count (86 × 109/l) with occasional macrothrombocytes (diameter 4-5 um) and a history of bruising easily. Several mutations in the amino terminal zinc finger domain of GATA-1 have been linked with thrombocytopenia and thalassemia or dsyerythropoietic anemia and the presence of macrothrombocytes. Our data provide evidence that mutations outside the zinc finger domain can affect GATA-1 functions in erythroid and megakaryocyte differentiation. In this case, the predicted extended carboxy terminus may interfere with GATA-1 interactions involving other DNA-binding proteins. Disclosures: No relevant conflicts of interest to declare.


Blood ◽  
2001 ◽  
Vol 98 (6) ◽  
pp. 1792-1801 ◽  
Author(s):  
Andrew C. Oates ◽  
Stephen J. Pratt ◽  
Brenda Vail ◽  
Yi-lin Yan ◽  
Robert K. Ho ◽  
...  

Abstract The Krüppel-like factor(KLF) family of genes encodes transcriptional regulatory proteins that play roles in differentiation of a diverse set of cells in mammals. For instance, the founding memberKLF1 (also known as EKLF) is required for normal globin production in mammals. Five new KLF genes have been isolated from the zebrafish, Danio rerio, and the structure of their products, their genetic map positions, and their expression during development of the zebrafish have been characterized. Three genes closely related to mammalian KLF2 andKLF4 were found, as was an ortholog of mammalianKLF12. A fifth gene, apparently missing from the genome of mammals and closely related to KLF1 and KLF2,was also identified. Analysis demonstrated the existence of novel conserved domains in the N-termini of these proteins. Developmental expression patterns suggest potential roles for these zebrafish genes in diverse processes, including hematopoiesis, blood vessel function, and fin and epidermal development. The studies imply a high degree of functional conservation of the zebrafish genes with their mammalian homologs. These findings further the understanding of theKLF genes in vertebrate development and indicate an ancient role in hematopoiesis for the Krüppel-like factorgene family.


2018 ◽  
Author(s):  
Hong Tan ◽  
Ruth E. Fulton ◽  
Wen-Hai Chou ◽  
Denise A. Birkholz ◽  
Meridee P. Mannino ◽  
...  

AbstractCell differentiation and cell fate determination in sensory systems are essential for stimulus discrimination and coding of environmental stimuli. Color vision is based on the differential color sensitivity of retinal photoreceptors, however the developmental programs that control photoreceptor cell differentiation and specify color sensitivity are poorly understood. In Drosophila melanogaster, there is evidence that the color sensitivity of different photoreceptors in the compound eye is regulated by inductive signals between cells, but the exact nature of these signals and how they are propagated remains unknown. We conducted a genetic screen to identify additional regulators of this process and identified a novel mutation in the hibris gene. hibris encodes an irre cell recognition module protein (IRM). These immunoglobulin super family cell adhesion molecules include human neph and nephrin (NPHS1). hibris is expressed dynamically in the developing Drosophila melanogaster eye and loss-of-function mutations give rise to a diverse range of mutant phenotypes including disruption of the specification of R8 photoreceptors cell diversity. The specification of blue or green sensitivity in R8 cells is also dependent upon Notch signaling. We demonstrate that hibris is required within the retina, non-cell autonomously for these effects, suggesting an additional layer of complexity in the signaling process that produces paired expression of opsin genes in adjacent R7 and R8 photoreceptor cells.Author SummaryAs humans, our ability to distinguish different colors is dependent upon the presence of three different types of cone cell neurons in the retina of the eye. The cone cells express blue, green or red absorbing visual pigments that detect and discriminate between these colors. The principle of color discrimination by neurons “tuned” to different colors is an evolutionarily conserved specialization that occurs in many different animals. This specialization requires 1) visual pigments that detect different colors and 2) a developmental program that regulates the expression of these pigments in different types of cells. In this study we discovered that the fruit fly (Drosophila melanogaster) gene hibris is required for the developmental program that produces blue sensitive neurons in the fly retina. When we over-expressed hibris throughout the developing retina, extra blue sensitive cells were produced. These results demonstrate that if there is not enough hibris, too few blue sensitive cells form, but if there is too much hibris, too many blue sensitive cells form. Finally, we discovered that the hibris gene does not act in color sensitive neurons of the retina themselves. This surprising discovery suggests that hibris may influence development of the retina in a completely new and different way.


Sign in / Sign up

Export Citation Format

Share Document