Early development will be studied in the mouse by the establishment of cell lineages in the pre-gastrulation embryo, and by the generation of insertional mutations affecting development in transgenic mice. In this work, mouse embryos will be infected with retroviruses at different stages of development. As a result, individual cells of the embryo will be labelled genetically, and the mosaicism thus generated will be used to follow cell lineages during early development. To facilitate tracking of the infected cells and their progeny, retroviral vectors introduced into mouse embryos will encode an easily identifiable and innocuous gene product, such as the bacterial beta galactosidase gene. Retroviruses will be introduced into preimplantation stage embryos, as well as in egg cylinder stage embryos, in order to establish a fate map of the mouse embryo prior to or at gastrulation. In particular, the origin of the germ line will be investigated. Mosaic animals will be bred with wild-type animals to generate transgenic strains containing a single proviral genome in the germ line. These strains will be analyzed to investigate the effect of parental imprinting on expression of the transgene, and to derive new retroviral-induced mutations. The proviruses will be used as tags to clone flanking genomic sequences and to identify the mutated genes. This approach should contribute to a better understanding of genes active during early development.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD024875-03
Application #
3325742
Study Section
Human Embryology and Development Subcommittee 1 (HED)
Project Start
1989-01-01
Project End
1993-12-31
Budget Start
1991-01-01
Budget End
1991-12-31
Support Year
3
Fiscal Year
1991
Total Cost
Indirect Cost
Name
Baylor College of Medicine
Department
Type
Schools of Medicine
DUNS #
074615394
City
Houston
State
TX
Country
United States
Zip Code
77030
Zou, Hongyan; Feng, Rui; Huang, Yong et al. (2015) Double minute amplification of mutant PDGF receptor ? in a mouse glioma model. Sci Rep 5:8468
Friedel, Roland H; Friedel, Caroline C; Bonfert, Thomas et al. (2013) Clonal expansion analysis of transposon insertions by high-throughput sequencing identifies candidate cancer genes in a PiggyBac mutagenesis screen. PLoS One 8:e72338
Olson, Lorin E; Soriano, Philippe (2011) PDGFR? signaling regulates mural cell plasticity and inhibits fat development. Dev Cell 20:815-26
Friedel, Roland H; Soriano, Philippe (2010) Gene trap mutagenesis in the mouse. Methods Enzymol 477:243-69
Raymond, Christopher S; Soriano, Philippe (2010) ROSA26Flpo deleter mice promote efficient inversion of conditional gene traps in vivo. Genesis 48:603-6
Wassarman, Paul M; Soriano, Philippe M (2010) Guide to techniques in mouse development. Preface. Methods Enzymol 476:xix
Olson, Lorin E; Soriano, Philippe (2009) Increased PDGFRalpha activation disrupts connective tissue development and drives systemic fibrosis. Dev Cell 16:303-13
Bush, Jeffrey O; Soriano, Philippe (2009) Ephrin-B1 regulates axon guidance by reverse signaling through a PDZ-dependent mechanism. Genes Dev 23:1586-99
Schmahl, Jennifer; Rizzolo, Kamran; Soriano, Philippe (2008) The PDGF signaling pathway controls multiple steroid-producing lineages. Genes Dev 22:3255-67
Davy, Alice; Soriano, Philippe (2007) Ephrin-B2 forward signaling regulates somite patterning and neural crest cell development. Dev Biol 304:182-93

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