The Experts below are selected from a list of 81 Experts worldwide ranked by ideXlab platform
Konrad Basler - One of the best experts on this subject based on the ideXlab platform.
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multiple requirements for the receptor serine threonine kinase thick veins reveal novel functions of tgf beta homologs during drosophila embryogenesis
Development, 1994Co-Authors: Markus Affolter, D Nellen, Ute Nussbaumer, Konrad BaslerAbstract:Differentiation of distinct cell types at specific locations within a developing organism depends largely on the ability of cells to communicate. A major class of signalling Proteins implicated in cell to cell communication is represented by members of the TGF beta superfamily. A corresponding class of transmembrane serine/threonine kinases has recently been discovered that act as cell surface receptors for ligands of the TGF beta superfamily. The product of the Drosophila gene decapentaplegic (dpp) encodes a TGF beta homolog that plays multiple roles during embryogenesis and the development of imaginal discs. Here we describe the complex expression pattern of thick veins (tkv), which encodes a receptor for dpp. We make use of tkv loss-of-function mutations to examine the consequences of the failure of embryonic cells to respond to dpp and/or other TGF beta homologs. We find that while maternal tkv product allows largely normal dorsoventral pattering of the embryo, zygotic tkv activity is indispensable for dorsal closure of the embryo after germ band retraction. Furthermore, tkv activity is crucial for patterning the visceral mesoderm; in the absence of functional tkv gene product, visceral mesoderm parasegment 7 cells fail to express Ultrabithorax, but instead accumulate Antennapedia Protein. The tkv receptor is therefore involved in delimiting the expression domains of homeotic genes in the visceral mesoderm. Interestingly, tkv mutants fail to establish a proper tracheal network. Tracheal braches formed by cells migrating in dorsal or ventral directions are absent in tkv mutants. The requirements for tkv in dorsal closure, visceral mesoderm and trachea development assign novel functions to dpp or a closely related member of the TGF beta superfamily.
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Multiple requirements for the receptor serine/threonine kinase thick veins reveal novel functions of TGF beta homologs during Drosophila embryogenesis
Development (Cambridge England), 1994Co-Authors: Markus Affolter, D Nellen, Ute Nussbaumer, Konrad BaslerAbstract:Differentiation of distinct cell types at specific locations within a developing organism depends largely on the ability of cells to communicate. A major class of signalling Proteins implicated in cell to cell communication is represented by members of the TGF beta superfamily. A corresponding class of transmembrane serine/threonine kinases has recently been discovered that act as cell surface receptors for ligands of the TGF beta superfamily. The product of the Drosophila gene decapentaplegic (dpp) encodes a TGF beta homolog that plays multiple roles during embryogenesis and the development of imaginal discs. Here we describe the complex expression pattern of thick veins (tkv), which encodes a receptor for dpp. We make use of tkv loss-of-function mutations to examine the consequences of the failure of embryonic cells to respond to dpp and/or other TGF beta homologs. We find that while maternal tkv product allows largely normal dorsoventral pattering of the embryo, zygotic tkv activity is indispensable for dorsal closure of the embryo after germ band retraction. Furthermore, tkv activity is crucial for patterning the visceral mesoderm; in the absence of functional tkv gene product, visceral mesoderm parasegment 7 cells fail to express Ultrabithorax, but instead accumulate Antennapedia Protein. The tkv receptor is therefore involved in delimiting the expression domains of homeotic genes in the visceral mesoderm. Interestingly, tkv mutants fail to establish a proper tracheal network. Tracheal braches formed by cells migrating in dorsal or ventral directions are absent in tkv mutants. The requirements for tkv in dorsal closure, visceral mesoderm and trachea development assign novel functions to dpp or a closely related member of the TGF beta superfamily.
Markus Affolter - One of the best experts on this subject based on the ideXlab platform.
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multiple requirements for the receptor serine threonine kinase thick veins reveal novel functions of tgf beta homologs during drosophila embryogenesis
Development, 1994Co-Authors: Markus Affolter, D Nellen, Ute Nussbaumer, Konrad BaslerAbstract:Differentiation of distinct cell types at specific locations within a developing organism depends largely on the ability of cells to communicate. A major class of signalling Proteins implicated in cell to cell communication is represented by members of the TGF beta superfamily. A corresponding class of transmembrane serine/threonine kinases has recently been discovered that act as cell surface receptors for ligands of the TGF beta superfamily. The product of the Drosophila gene decapentaplegic (dpp) encodes a TGF beta homolog that plays multiple roles during embryogenesis and the development of imaginal discs. Here we describe the complex expression pattern of thick veins (tkv), which encodes a receptor for dpp. We make use of tkv loss-of-function mutations to examine the consequences of the failure of embryonic cells to respond to dpp and/or other TGF beta homologs. We find that while maternal tkv product allows largely normal dorsoventral pattering of the embryo, zygotic tkv activity is indispensable for dorsal closure of the embryo after germ band retraction. Furthermore, tkv activity is crucial for patterning the visceral mesoderm; in the absence of functional tkv gene product, visceral mesoderm parasegment 7 cells fail to express Ultrabithorax, but instead accumulate Antennapedia Protein. The tkv receptor is therefore involved in delimiting the expression domains of homeotic genes in the visceral mesoderm. Interestingly, tkv mutants fail to establish a proper tracheal network. Tracheal braches formed by cells migrating in dorsal or ventral directions are absent in tkv mutants. The requirements for tkv in dorsal closure, visceral mesoderm and trachea development assign novel functions to dpp or a closely related member of the TGF beta superfamily.
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Multiple requirements for the receptor serine/threonine kinase thick veins reveal novel functions of TGF beta homologs during Drosophila embryogenesis
Development (Cambridge England), 1994Co-Authors: Markus Affolter, D Nellen, Ute Nussbaumer, Konrad BaslerAbstract:Differentiation of distinct cell types at specific locations within a developing organism depends largely on the ability of cells to communicate. A major class of signalling Proteins implicated in cell to cell communication is represented by members of the TGF beta superfamily. A corresponding class of transmembrane serine/threonine kinases has recently been discovered that act as cell surface receptors for ligands of the TGF beta superfamily. The product of the Drosophila gene decapentaplegic (dpp) encodes a TGF beta homolog that plays multiple roles during embryogenesis and the development of imaginal discs. Here we describe the complex expression pattern of thick veins (tkv), which encodes a receptor for dpp. We make use of tkv loss-of-function mutations to examine the consequences of the failure of embryonic cells to respond to dpp and/or other TGF beta homologs. We find that while maternal tkv product allows largely normal dorsoventral pattering of the embryo, zygotic tkv activity is indispensable for dorsal closure of the embryo after germ band retraction. Furthermore, tkv activity is crucial for patterning the visceral mesoderm; in the absence of functional tkv gene product, visceral mesoderm parasegment 7 cells fail to express Ultrabithorax, but instead accumulate Antennapedia Protein. The tkv receptor is therefore involved in delimiting the expression domains of homeotic genes in the visceral mesoderm. Interestingly, tkv mutants fail to establish a proper tracheal network. Tracheal braches formed by cells migrating in dorsal or ventral directions are absent in tkv mutants. The requirements for tkv in dorsal closure, visceral mesoderm and trachea development assign novel functions to dpp or a closely related member of the TGF beta superfamily.
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NMR structure determination reveals that the homeodomain is connected through a flexible linker to the main body in the Drosophila Antennapedia Protein
Proceedings of the National Academy of Sciences of the United States of America, 1992Co-Authors: Yan Qiu Qian, Walter J. Gehring, Gottfried Otting, Katsuo Furukubo-tokunaga, Markus Affolter, Kurt WüthrichAbstract:The secondary structure of an N-terminally elongated Antennapedia (Antp) homeodomain (HD) polypeptide containing residues -14 to 67, where residues 1-60 constitute the HD, has been determined by NMR in solution. This polypeptide contains the conserved motif -Tyr-Pro-Trp-Met- (YPWM) at positions -9 to -6. Despite the hydrophobic nature of this tetrapeptide motif, the N-terminal arm consisting of residues -14 to 6 is flexibly disordered, and the well-defined part of the HD structure with residues 7-59 is indistinguishable from that of the shorter Antp HD polypeptide (where positions 0, 1, and 67 are methionine, arginine, and glycine, respectively). In vitro biochemical studies showed that the stability and specificity of the DNA binding previously observed for the shorter Antp HD polypeptide is preserved in the elongated polypeptide. These results strongly support the view that the HD is connected through a flexible linker to the main body in the Antp Protein and that the minor groove contacts by the N-terminal arm (residues 1-6) in the Antp HD-DNA complex are an intrinsic feature of the DNA-binding interactions of the intact Antp Protein.
Joseph Desimone - One of the best experts on this subject based on the ideXlab platform.
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A homeodomain Protein binds to. gamma. -globin gene regulatory sequences
Proceedings of the National Academy of Sciences of the United States of America, 1991Co-Authors: Donald Lavelle, Janice Ducksworth, Georgina Gomes, Eva M. Eves, Michael Keller, Paul Heller, Joseph DesimoneAbstract:Abstract Developmental regulation of gamma-globin gene expression probably occurs through developmental-stage-specific trans-acting factors able to promote the interaction of enhancer elements located in the far upstream locus control region with regulatory elements in the gamma gene promoters and 3' A gamma enhancer located in close proximity to the genes. We have detected a nuclear Protein in K562 and baboon fetal bone marrow nuclear extracts capable of binding to A+T-rich sequences in the locus control region, gamma gene promoter, and 3' A gamma enhancer. SDS/polyacrylamide gel analysis of the purified K562 binding activity revealed a single Protein of 87 kDa. A K562 cDNA clone was isolated encoding a beta-galactosidase fusion Protein with a DNA binding specificity identical to that of the K562/fetal bone marrow nuclear Protein. The cDNA clone encodes a homeodomain homologous to the Drosophila Antennapedia Protein.
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A homeodomain Protein binds toy-globin gene regulatory sequences
1991Co-Authors: Janice Ducksworth, Georgina Gomes, Joseph DesimoneAbstract:Developmental regulation ofy-globin gene expression probably occurs through developmental-stage- specific trans-acting factors able topromote theinteraction of enhancer elements located inthefarupstream locus control region with regulatory elements intheygenepromoters and3' Atenhancer located inclose proximity tothegenes. Wehave detected anuclear Protein inK562andbaboon fetal bone marrownuclear extracts capable ofbinding toA+T-rich sequences inthelocus control region, ygenepromoter, and3' A7enhancer. SDS/polyacrylamide gelanalysis ofthepurified K562binding activity revealed asingle Protein of87kDa.A K562cDNAclone wasisolated encoding afi-galactosidase fusion Protein withaDNAbinding specificity identical tothat oftheK562/fetal bonemarrownuclear Protein. ThecDNA clone encodes ahomeodomain homologous totheDrosophila Antennapedia Protein. developmental-stage-specific factor presumably mediating this interaction inchickens hasbeendemonstrated (15). Thebinding oferythroid andtissue-ubiquitous factors to sequences present inthey-globin promoter (16-21), the humanP-globin promoter (22), andthehumanf3-globin 3' enhancer (23)havebeendescribed. No developmental- specific factor forthehumanglobin genehasbeenreported (13). We describe afactor inK562andfetal baboon bone marrow(BM)nuclear extracts binding specifically tose- quences inthe3'Aly enhancer, y-globin promoter, andLCR. Aclone obtained fromaAgtll K562cDNAlibrary expresses af-galactosidase (J-gal) fusion Protein that isalsoableto bindspecifically tothese sequences. ThecDNAinsert ofthis clone encodes ahomeodomain homologous totheDrosophila Antennapedia Protein.*
Elettra Ronchi - One of the best experts on this subject based on the ideXlab platform.
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Promoter-specific regulation of gene expression by an exogenously added homeodomain that promotes neurite growth
FEBS Letters, 1995Co-Authors: Isabelle Le Roux, Michel Volovitch, Alain Prochiantz, Sandra Duharcourt, Elettra RonchiAbstract:pAntp, a 60 amino acid long peptide corresponding to the homeodomain of the Drosophila Antennapedia Protein, translocates through neuronal membranes when added exogenously to neurons in culture, where it accumulates in the nucleus and promotes neurite outgrowth. We proposed that the peptide, once internalized, may compete for homeoProtein DNA binding sites. To investigate this point, we have produced a permanent fibroblast cell line which carries a luciferase reporter gene under the control of a 93 bp genomic region of the HOXD9 promoter with binding sites for homeoProteins. Externally added pAntp specifically down‐regulates the expression of the reporter gene, suggesting that the neurotrophic effects observed previously are mediated by direct binding of pAntp to homeoProtein target sites
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Promoter‐specific regulation of gene expression by an exogenously added homeodomain that promotes neurite growth
FEBS letters, 1995Co-Authors: Isabelle Le Roux, Michel Volovitch, Alain Prochiantz, Sandra Duharcourt, Elettra RonchiAbstract:pAntp, a 60 amino acid long peptide corresponding to the homeodomain of the Drosophila Antennapedia Protein, translocates through neuronal membranes when added exogenously to neurons in culture, where it accumulates in the nucleus and promotes neurite outgrowth. We proposed that the peptide, once internalized, may compete for homeoProtein DNA binding sites. To investigate this point, we have produced a permanent fibroblast cell line which carries a luciferase reporter gene under the control of a 93 bp genomic region of the HOXD9 promoter with binding sites for homeoProteins. Externally added pAntp specifically down-regulates the expression of the reporter gene, suggesting that the neurotrophic effects observed previously are mediated by direct binding of pAntp to homeoProtein target sites.
Isabelle Le Roux - One of the best experts on this subject based on the ideXlab platform.
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Promoter-specific regulation of gene expression by an exogenously added homeodomain that promotes neurite growth
FEBS Letters, 1995Co-Authors: Isabelle Le Roux, Michel Volovitch, Alain Prochiantz, Sandra Duharcourt, Elettra RonchiAbstract:pAntp, a 60 amino acid long peptide corresponding to the homeodomain of the Drosophila Antennapedia Protein, translocates through neuronal membranes when added exogenously to neurons in culture, where it accumulates in the nucleus and promotes neurite outgrowth. We proposed that the peptide, once internalized, may compete for homeoProtein DNA binding sites. To investigate this point, we have produced a permanent fibroblast cell line which carries a luciferase reporter gene under the control of a 93 bp genomic region of the HOXD9 promoter with binding sites for homeoProteins. Externally added pAntp specifically down‐regulates the expression of the reporter gene, suggesting that the neurotrophic effects observed previously are mediated by direct binding of pAntp to homeoProtein target sites
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Promoter‐specific regulation of gene expression by an exogenously added homeodomain that promotes neurite growth
FEBS letters, 1995Co-Authors: Isabelle Le Roux, Michel Volovitch, Alain Prochiantz, Sandra Duharcourt, Elettra RonchiAbstract:pAntp, a 60 amino acid long peptide corresponding to the homeodomain of the Drosophila Antennapedia Protein, translocates through neuronal membranes when added exogenously to neurons in culture, where it accumulates in the nucleus and promotes neurite outgrowth. We proposed that the peptide, once internalized, may compete for homeoProtein DNA binding sites. To investigate this point, we have produced a permanent fibroblast cell line which carries a luciferase reporter gene under the control of a 93 bp genomic region of the HOXD9 promoter with binding sites for homeoProteins. Externally added pAntp specifically down-regulates the expression of the reporter gene, suggesting that the neurotrophic effects observed previously are mediated by direct binding of pAntp to homeoProtein target sites.