Progression of the morphogenetic furrow in the Drosophila eye: the roles of Hedgehog, Decapentaplegic and the Raf pathway

Development ◽  
1999 ◽  
Vol 126 (24) ◽  
pp. 5795-5808 ◽  
Author(s):  
S. Greenwood ◽  
G. Struhl
Keyword(s):  
Transcription Factor ◽  
Short Range ◽  
Morphogenetic Furrow ◽  
Serine Threonine Kinase ◽  
Present Evidence ◽  
Threonine Kinase ◽  
Drosophila Eye ◽  
Undifferentiated Cells ◽  
Hh Signaling ◽  
Necessary And Sufficient

During Drosophila eye development, Hedgehog (Hh) protein secreted by maturing photoreceptors directs a wave of differentiation that sweeps anteriorly across the retinal primordium. The crest of this wave is marked by the morphogenetic furrow, a visible indentation that demarcates the boundary between developing photoreceptors located posteriorly and undifferentiated cells located anteriorly. Here, we present evidence that Hh controls progression of the furrow by inducing the expression of two downstream signals. The first signal, Decapentaplegic (Dpp), acts at long range on undifferentiated cells anterior to the furrow, causing them to enter a ‘pre-proneural’ state marked by upregulated expression of the transcription factor Hairy. Acquisition of the pre-proneural state appears essential for all prospective retinal cells to enter the proneural pathway and differentiate as photoreceptors. The second signal, presently unknown, acts at short range and is transduced via activation of the Serine-Threonine kinase Raf. Activation of Raf is both necessary and sufficient to cause pre-proneural cells to become proneural, a transition marked by downregulation of Hairy and upregulation of the proneural activator, Atonal (Ato), which initiates differentiation of the R8 photoreceptor. The R8 photoreceptor then organizes the recruitment of the remaining photoreceptors (R1-R7) through additional rounds of Raf activation in neighboring pre-proneural cells. Finally, we show that Dpp signaling is not essential for establishing either the pre-proneural or proneural states, or for progression of the furrow. Instead, Dpp signaling appears to increase the rate of furrow progression by accelerating the transition to the pre-proneural state. In the abnormal situation in which Dpp signaling is blocked, Hh signaling can induce undifferentiated cells to become pre-proneural but does so less efficiently than Dpp, resulting in a retarded rate of furrow progression and the formation of a rudimentary eye.

scholarly journals Regulation of the forkhead transcription factor FKHR, but not the PAX3-FKHR fusion protein, by the serine/threonine kinase Akt

Oncogene ◽  
1999 ◽  
Vol 18 (51) ◽  
pp. 7328-7333 ◽  
Author(s):  
Luis del Peso ◽  
Víctor M González ◽  
Rubén Hernández ◽  
Frederic G Barr ◽  
Gabriel Núñez
Keyword(s):  
Transcription Factor ◽  
Fusion Protein ◽  
Forkhead Transcription Factor ◽  
Serine Threonine Kinase ◽  
Threonine Kinase

PRKD2 Serine-Threonine Kinase, a Downstream Effector Of GABP, Plays Essential Roles For The Maintenance Of HSCs

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2430-2430
Author(s):  
Zhong-Fa Yang ◽  
Wang Junling ◽  
Alan G. Rosmarin
Keyword(s):  
Bone Marrow ◽  
Transcription Factor ◽  
Protein Kinase ◽  
Bone Marrow Cells ◽  
Specific Cell ◽  
Wild Type ◽  
Serine Threonine Kinase ◽  
Hematopoietic Stem ◽  
Threonine Kinase ◽  
Marrow Cells

Abstract Hematopoietic stem cells (HSCs) are the source of all blood lineages, and HSCs must balance quiescence, self-renewal, and differentiation to meet lifelong needs for blood cell development. GABP is an ets-related transcription factor that controls critical genes in myeloid and lymphoid development, and has been implicated in control of HSC growth. GABP is an obligate multimeric transcription factor that includes the DNA-binding ets component, GABPa, along with various GABPb partner proteins. We conditionally deleted Gabpa in mouse bone marrow and found that Gabpa cells have a profound growth disadvantage due to cell cycle arrest in HSCs. We identified Protein Kinase D2 (PRKD2) as a candidate effector of GABP. PRKD2 is a diacyl glycerol- and Protein Kinase C-activated serine-threonine kinase, because deletion of Gabpa markedly reduced PRKD2 expression in normal HSCs and progenitor cells. In a Prkd2ki/ki mouse model, in which two functionally essential phosphorylation serines were inactivated genetically, their bone marrow long term HSCs reduced dramatically and the short term HSCs increased accordingly. Mice transplanted with a 1:1 mixture of Prkd2ki/ki and wild type bone marrow cells demonstrated the decreased proportion of the Prkd2ki/ki bone marrow cells with the corresponding increase of the wild type cells. Although ectopic expression of the human Chronic Myeloid Leukemia (CML) fusion oncogene BCR-ABL in wild type bone marrow cells induced rapid CML development, expression of BCR-ABL in Prkd2ki/ki bone marrow cells failed to develop CML in transplanted recipient mice. Analysis of the peripheral blood, bone marrow and spleen of these mice revealed that the BCR-ABL+, Prkd2ki/ki cells did not express myeloid or lymphoid specific cell surface antigens CD11b, Gr1, B220, or CD3e. They demonstrated an immature blast-like microscopic morphology, and recipient mice transplanted with these cells died before the onset of CML development. We conclude that the phosphorylation activated Prkd2 is required for the maintenance of HSC pool and the development of mature hematopoietic lineages from HSCs. These findings suggest that PRKD2 kinase mediate key downstream events of both PKC and transcription factor GABP, and that PRKD2 may serve as a novel therapeutic target in leukemia. Disclosures: No relevant conflicts of interest to declare.

Short-range positional signals in the developing Drosophila eye

Development ◽  
1989 ◽  
Vol 107 (Supplement) ◽  
pp. 59-63
Author(s):  
Andrew Tomlinson
Keyword(s):  
Transcription Factor ◽  
Tyrosine Kinase ◽  
Gene Product ◽  
Short Range ◽  
Gene Products ◽  
Molecular Approach ◽  
Drosophila Eye

Positional signals provided by immediate neighbours appear to direct developmental decisions in the eye of Drosophila. By a combined genetic and molecular approach the biochemical bases of the signal and reception mechanisms are being systematically dissected. Three key gene products have now been identified, sevenless is a transmembrane tyrosine kinase probably transducing positional signals that direct the R7 cell to its fate. The bride of sevenless gene product is on the signalling side of the mechanism and is required in R8 for R7 to develop. The type of protein bride of sevenless encodes is not yet known. The rough gene encodes a transcription factor on the signalling side required in R2 and R5 for positional signals to be transmitted to neighbouring cells.

Shortsighted acts in the decapentaplegic pathway in Drosophila eye development and has homology to a mouse TGF-beta-responsive gene

Development ◽  
1995 ◽  
Vol 121 (9) ◽  
pp. 2835-2845 ◽  
Author(s):  
J.E. Treisman ◽  
Z.C. Lai ◽  
G.M. Rubin
Keyword(s):  
Leucine Zipper ◽  
Optic Lobe ◽  
Tgf Beta ◽  
Morphogenetic Furrow ◽  
Differentiated Cells ◽  
Drosophila Eye ◽  
Undifferentiated Cells ◽  
Leucine Zipper Protein ◽  
Eye Imaginal Disc ◽  
The Brain

Differentiation in the Drosophila eye imaginal disc traverses the disc as a wave moving from posterior to anterior. The propagation of this wave is driven by hedgehog protein secreted by the differentiated cells in the posterior region of the disc. Hedgehog induces decapentaplegic expression at the front of differentiation, in the morphogenetic furrow. We have identified a gene, shortsighted, which is expressed in a hedgehog-dependent stripe in the undifferentiated cells just anterior to the furrow and which appears to be involved in the transmission of the differentiation-inducing signal; a reduction in shortsighted function leads to a delay in differentiation and to a loss of photoreceptors in the adult. shortsighted is also required for a morphogenetic movement in the brain that reorients the second optic lobe relative to the first. shortsighted encodes a cytoplasmic leucine zipper protein with homology to a mouse gene, TSC-22, which is transcriptionally induced in response to TGF-beta.

PRKD2 Serine-Threonine Kinase, an Essential Effector of Gabp Transcription Factor, Is Required for Development of Chronic Myelogenous Leukemia

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1672-1672
Author(s):  
Zhong-Fa Yang ◽  
Haojian Zhang ◽  
Leyuan Ma ◽  
Cong Peng ◽  
Yaoyu Chen ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Bone Marrow ◽  
Transcription Factor ◽  
Protein Kinase ◽  
Chronic Myelogenous Leukemia ◽  
Myeloid Cell ◽  
Myelogenous Leukemia ◽  
Serine Threonine Kinase ◽  
Threonine Kinase ◽  
Cell Cycle Entry

Abstract Abstract 1672 Chronic Myelogenous Leukemia (CML) is a myeloproliferative neoplasm (MPN) caused by transformation of hematopoietic stem cells (HSCs) by the BCR-ABL oncogene. CML is associated with excessive proliferation of HSCs and massive expansion of the myeloid cell pool. GABP is an ets-related transcription factor that controls critical genes in myeloid and lymphoid development, and has been implicated in control of HSC growth. GABP is an obligate multimeric transcription factor that includes the DNA-binding ets component, GABPα, along with various GABPβ partner proteins. We conditionally deleted Gabpa in mouse bone marrow and found that Gabpa cells have a profound growth disadvantage due to cell cycle arrest in HSCs. In a mouse model of CML, animals transplanted with BCR-ABL-infected bone marrow developed massive myeloid cell expansion and died with a MPN. Induced deletion of Gabpa prevented development of CML, yet mice continued to produce mature BCR-ABL-expressing granulocytes for months without apparent illness. BCR-ABL+ cells were transplantable into secondary recipients without development of CML, and contributed to all hematopoietic lineages, thereby confirming expression of BCR-ABL by long-term HSCs. We used a bioinformatic approach to analyze GABP-bound genes that are upregulated in both human and mouse LSCs compared to normal HSCs. Among 115 GABP-bound, CML-associated genes, we identified Protein Kinase D2 (PRKD2) as a candidate effector of GABP. PRKD2 is a diacyl glycerol- and Protein Kinase C-activated serine-threonine kinase that has been implicated in cancer, but has not previously been associated with HSC functions or CML. Deletion of Gabpa markedly reduced PRKD2 expression in normal HSCs and progenitor cells. In vitro growth of BCR-ABL+ bone marrow cells was prevented by Gabpa deletion, but growth was partially rescued by forced expression of PRKD2. Knockdown and pharmacologic inhibition of PRKD2 blocked cell cycle entry of BCR-ABL+ cells. We conclude that Gabp is required for HSC cell cycle entry and for development of CML, and that these effects of GABP are mediated, in part, by PRKD2. These findings suggest that PRKD2 kinase may serve as a novel therapeutic target in leukemia. Disclosures: No relevant conflicts of interest to declare.

Beneficial effects of IL-1 cytokine inactivation and the role of the serine/threonine kinase MK-2 in hepatic steatosis in a murine obesity model

2015 ◽  
Vol 53 (12) ◽  
Author(s):  
J Wohlfahrt ◽  
A Fettelschoss ◽  
T Kündig ◽  
H Hermanns ◽  
B Müllhaupt ◽  
...  
Keyword(s):  
Hepatic Steatosis ◽  
Serine Threonine Kinase ◽  
Threonine Kinase ◽  
Beneficial Effects
Sign in / Sign up

Export Citation Format

Share Document