Biomedical subjects

K Staehling-Hampton

Publications and source records attributed to K Staehling-Hampton.

8 recordsLinked to original sources

PubMed2000

A role for Ebi in neuronal cell cycle control.

Mutations in ebi were isolated as enhancers of an over-proliferation phenotype generated by elevated E2F/DP activity in the Drosophila eye. ebi alleles also strongly suppress a phenotype caused by the cyclin-dependent kinase inhibitor p21, restoring S phases in the second mitotic wave of the developing eye disk. ebi mutant embryos display ectopic S phases within the peripheral nervous system and central nervous system at a time in development when neuronal precursor cells would normally begin to differentiate. Consistent with this, we find that ebi mutants have a reduced capacity to undergo neuronal differentiation, that Ebi physically interacts with Sina and phyllopod, and that Ebi promotes Ttk88 degradation in vitro and in S2 cells. Ectopic expression of Ttk88 inhibited differentiation in embryos and eye discs; however, this block to differentiation was insufficient to promote S phase entry in either of the situations where ebi mutations gave this effect. We conclude that Ebi has two distinct functions; it promotes the degradation of a repressor of neuronal differentiation (Ttk88), and has a second independent function that limits S phase entry.

Alleles↗

PubMed1999

A genetic screen for modifiers of E2F in Drosophila melanogaster.

The activity of the E2F transcription factor is regulated in part by pRB, the protein product of the retinoblastoma tumor suppressor gene. Studies of tumor cells show that the p16(ink4a)/cdk4/cyclin D/pRB pathway is mutated in most forms of cancer, suggesting that the deregulation of E2F, and hence the cell cycle, is a common event in tumorigenesis. Extragenic mutations that enhance or suppress E2F activity are likely to alter cell-cycle control and may play a role in tumorigenesis. We used an E2F overexpression phenotype in the Drosophila eye to screen for modifiers of E2F activity. Coexpression of dE2F and its heterodimeric partner dDP in the fly eye induces S phases and cell death. We isolated 33 enhancer mutations of this phenotype by EMS and X-ray mutagenesis and by screening a deficiency library collection. The majority of these mutations sorted into six complementation groups, five of which have been identified as alleles of brahma (brm), moira (mor) osa, pointed (pnt), and polycephalon (poc). osa, brm, and mor encode proteins with homology to SWI1, SWI2, and SWI3, respectively, suggesting that the activity of a SWI/SNF chromatin-remodeling complex has an important impact on E2F-dependent phenotypes. Mutations in poc also suppress phenotypes caused by p21(CIP1) expression, indicating an important role for polycephalon in cell-cycle control.

Animals↗

PubMed1995

Drosophila Dpp signaling is mediated by the punt gene product: a dual ligand-binding type II receptor of the TGF beta receptor family.

Signaling by TGF beta-related factors requires ligand-induced association between type I and type II transmembrane serine/threonine kinases. In Drosophila, the saxophone (sax) and thick veins (tkv) genes encode type I receptors that mediate signaling by decapentaplegic (dpp), a member of the bone morphogenetic protein (BMP) subgroup of TGF beta-type factors. In this report, we demonstrate that the Drosophila punt gene encodes atr-II, a previously described type II receptor that on its own is able to bind activin but not BMP2, a vertebrate ortholog of dpp. Mutations in punt produce phenotypes similar to those exhibited by tkv, sax, and dpp mutants. Furthermore, punt will bind BMP2 in concert with tkv or sax, forming complexes with these receptors. We suggest that punt functions as a type II receptors for dpp and propose that BMP signaling in vertebrates may also involve sharing of type II receptors by diverse ligands.

Activin Receptors↗

PubMed1995

A Drosophila protein related to the human zinc finger transcription factor PRDII/MBPI/HIV-EP1 is required for dpp signaling.

Little is known about the signal transduction pathways by which cells respond to mammalian TGF-beta s or to decapentaplegic (dpp), a Drosophila TGF-beta-related factor. Here we describe the genetic and molecular characterization of Drosophila schnurri (shn), a putative transcription factor implicated in dpp signaling. The shn protein has eight zinc fingers and is related to a human transcription factor, PRDII/MBPI/HIV-EP1, that binds to nuclear factor-kappa B-binding sites and activates transcription from the HIV long terminal repeat (LTR). shn mRNA is expressed in a dynamic pattern in the embryo that includes most of the known target tissues of dpp, including the dorsal blastoderm, the mesodermal germlayer and parasegments 4 and 7 of the midgut. Mutations in shn affect several developmental processes regulated by dpp including induction of visceral mesoderm cell fate, dorsal/ventral patterning of the lateral ectoderm and wing vein formation. Absence of shn function blocks the expanded expression of the homeodomain protein bagpipe in the embryonic mesoderm caused by ectopic dpp expression, illustrating a requirement for shn function downstream of dpp action. We conclude that shn function is critical for cells to respond properly to dpp and propose that shn protein is the first identified downstream component of the signal transduction pathway used by dpp and its receptors.

Amino Acid Sequence↗

PubMed1994

Identification of two bone morphogenetic protein type I receptors in Drosophila and evidence that Brk25D is a decapentaplegic receptor.

Drosophila sequences at chromosomal positions 25D (Brk25D) and 43E (Brk43E) are similar to the TGF beta type I receptor serine/threonine kinases and are expressed broadly during embryogenesis. Brk25D binds dpp protein and bone morphogenetic protein 2 with high affinity. Mutations affecting Brk25D map to the gene thick veins and block the expression of two decapentaplegic-responsive (dpp-responsive) genes, dpp and labial, in the embryonic midgut. Defects in Brk25D receptor function combined with reduced expression of dpp ligand produce mutant phenotypes in the embryo and adult. Brk43E is the product of the gene saxophone, which also interacts with dpp. We conclude that dpp signaling in vivo is mediated by at least two receptors, Brk25D and Brk43E.

Amino Acid Sequence↗

PubMed1994

Ectopic decapentaplegic in the Drosophila midgut alters the expression of five homeotic genes, dpp, and wingless, causing specific morphological defects.

The patterns of homeotic gene expression in the Drosophila midgut visceral mesoderm are instrumental in several morphogenetic events, including the formation of the gastric caeca and the positioning of the three midgut constrictions. We demonstrate that a potent regulator of homeotic gene expression in the visceral mesoderm is the secreted growth factor-like molecule encoded by the decapentaplegic (dpp) gene. Ectopic dpp in the visceral mesoderm caused changes in the gene expression of Sex combs reduced, Antennapedia, Ultrabithorax (Ubx), and abdominal-A (abd-A) and disrupted the formation of the gastric caeca and the first and third midgut constrictions. Ectopic dpp also induced expression of teashirt, wingless (wg) and the endogenous dpp gene in the visceral mesoderm and enhanced labial expression in the adjacent endoderm. The patterns of gene expression and the formation of the second midgut constriction in the presence of ectopic dpp are most consistent with a dpp-induced transformation of virtually the entire midgut to cell fates normally seen only in the parasegment (ps)7 and ps8 regions of the midgut. We conclude that dpp is a primary signal in maintaining Ubx expression in the visceral mesoderm in a pattern different from Ubx expression in the embryonic ectoderm and in providing a cell-cell communication mechanism by which Ubx expression influences gene expression across germlayers and across the ps7 to ps8 parasegment boundary in the visceral mesoderm.

Animals↗

PubMed1994

Specificity of bone morphogenetic protein-related factors: cell fate and gene expression changes in Drosophila embryos induced by decapentaplegic but not 60A.

Reported assays of the bone morphogenetic proteins (BMPs) have not in general revealed specific functions for the different proteins, belying the specificity implied by the evolutionary conservation and distinct expression patterns of the genes encoding BMPs. We have used assays of developmental function to show that the two Drosophila homologues of the BMPs, decapentaplegic (dpp) and 60A, that both induce ectopic bone formation in mammalian assay systems, have distinct effects in Drosophila development. A binary expression system using the yeast transcriptional activator GAL4 directed identical patterns of tissue and temporally specific dpp and 60A expression. When dpp enhancer elements drove GAL4 expression, GAL4-responsive dpp transgenes rescued dpp mutant phenotypes, but GAL4-responsive 60A transgenes did not. Ectopic ectodermal expression of dpp during gastrulation respecified the dorsal/ventral pattern of the embryo. In contrast, ectopic 60A expression had no detectable effects on embryonic development but led to defects in adult structures or lethality during metamorphosis. Expression of 60A in cells expressing dpp did not interfere with dpp functions, indicating that dysfunctional heterodimers did not form at sufficient levels to inhibit dpp. These specific developmental responses in Drosophila indicate that in vivo functions of BMP-like factors can be more specific than indicated by the ectopic bone formation assays and that the Drosophila embryo provides an assay system sensitive to the structural differences that contribute to BMP specificity in vivo.

Amino Acid Sequence↗

PubMedDate not supplied

dpp induces mesodermal gene expression in Drosophila.

Inductive interactions between germ layers are an essential feature of the development of many organisms. In several species these interactions are mediated by members of the transforming growth factor-beta (TGF beta) family. In amphibians, different concentrations of activin can induce different types of mesoderm in the animal cap assay. In Drosophila, a member of the TGF beta family, decapentaplegic (dpp), acts as an inductive signal. Midway through embryogenesis, dpp is expressed in the visceral mesoderm, and enhances the expression of the homeotic gene labial in the underlying midgut endoderm. Earlier in development, however, dpp expression is limited to the dorsal ectoderm. At this stage in development, thickveins, a dpp receptor, is expressed in the mesoderm, and this suggests that ectodermal dpp might not only be required for development of dorsal ectoderm, but could also act inductively to mediate pattern formation in the underlying mesoderm. Here we show, by expressing dpp ectopically in the ectoderm and mesoderm and by examining dpp null mutant embryos, that dpp regulates expression of mesodermal genes.

Animals↗