We have recently identified a novel family of developmentally controlled genes in the frog Xenopus laevis. We demonstrated for the first time that, using a conserved region of Drosophila development-controlling genes called the homeobox, it was possible to identify and isolate vertebrate genes that resemble the Drosophila genes in several respects. Since then, similar genes have been isolated by others from a number of vertebrates, including cDNA clones from human transformed cells. We have by now isolated one of the largest collections of homeobox-containing cDNA clones available in any vertebrate, which are expressed at the gastrula stage of development. Some of these genes are expressed maternally in the oocyte and will be the focus of our studies, because they could potentially be examples of the elusive """"""""cytoplasmic determinants"""""""" thought to be laid down in egg cytoplasm for the control of the initial steps of embryonic differentiation. The objective of this proposal is to ascertain the developmental function of Xenopus homeobox-containing genes. A variety of techniques will be utilized towards this goal, and many of them take advantage of the ready availability of large amounts of Xenopus embryos during the earliest developmental stages, during which equivalent experiments with mammalian embryos would be much more difficult.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD021502-05
Application #
3320386
Study Section
Molecular Biology Study Section (MBY)
Project Start
1986-04-01
Project End
1991-03-31
Budget Start
1990-04-01
Budget End
1991-03-31
Support Year
5
Fiscal Year
1990
Total Cost
Indirect Cost
Name
University of California Los Angeles
Department
Type
Schools of Medicine
DUNS #
119132785
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Kim, Hyunjoon; Vick, Philipp; Hedtke, Joshua et al. (2015) Wnt Signaling Translocates Lys48-Linked Polyubiquitinated Proteins to the Lysosomal Pathway. Cell Rep 11:1151-9
Ploper, Diego; Taelman, Vincent F; Robert, Lidia et al. (2015) MITF drives endolysosomal biogenesis and potentiates Wnt signaling in melanoma cells. Proc Natl Acad Sci U S A 112:E420-9
Colozza, Gabriele; De Robertis, Edward M (2014) Maternal syntabulin is required for dorsal axis formation and is a germ plasm component in Xenopus. Differentiation 88:17-26
Demagny, Hadrien; Araki, Tatsuya; De Robertis, Edward M (2014) The tumor suppressor Smad4/DPC4 is regulated by phosphorylations that integrate FGF, Wnt, and TGF-? signaling. Cell Rep 9:688-700
Plouhinec, Jean-Louis; Zakin, Lise; Moriyama, Yuki et al. (2013) Chordin forms a self-organizing morphogen gradient in the extracellular space between ectoderm and mesoderm in the Xenopus embryo. Proc Natl Acad Sci U S A 110:20372-9
Dobrowolski, Radek; Vick, Philipp; Ploper, Diego et al. (2012) Presenilin deficiency or lysosomal inhibition enhances Wnt signaling through relocalization of GSK3 to the late-endosomal compartment. Cell Rep 2:1316-28
Ploper, Diego; Lee, Hojoon X; De Robertis, Edward M (2011) Dorsal-ventral patterning: Crescent is a dorsally secreted Frizzled-related protein that competitively inhibits Tolloid proteases. Dev Biol 352:317-28
Vorwald-Denholtz, Peggy P; De Robertis, Edward M (2011) Temporal pattern of the posterior expression of Wingless in Drosophila blastoderm. Gene Expr Patterns 11:456-63
Dobrowolski, Radek; De Robertis, Edward M (2011) Endocytic control of growth factor signalling: multivesicular bodies as signalling organelles. Nat Rev Mol Cell Biol 13:53-60
Eivers, Edward; Demagny, Hadrien; Choi, Renee H et al. (2011) Phosphorylation of Mad controls competition between wingless and BMP signaling. Sci Signal 4:ra68

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