The overall goal of the Program Project is to elucidate the complex interactions between the cellular and genetic control mechanisms which regulate the early stages of mammalian development. During the series of cleavage division which leads from zygote to blastocyst, sequential activation of the embryonic genome occurs concomitantly with the first overt signs of differentiation of trophectoderm and the origins of embryonic tissues. By the blastocyst stage, the embryo contains the lineage precursors of all embryonic and extraembryonic tissues. To determine the nature of these early and crucial differentiation events, we propose the following experimental approaches: 1) Through the joint effort of all investigators, genetic probes which reflect the gene expression at each developmental stage will be developed. These probes will be used to identify the corresponding gene products and to begin the analysis of their function. 2) By transient or permanent introduction into embryos of specific genes and/or their products, the functional role of these genes will be determined. 3) Nuclear transfer embryos will be analysed to determine the reasons for their developmental failure and for identifying the genes involved. Part of this approach will involve analysis of specific and gene regulation during gametogenesis. 4) The role of growth controlling molecules (including growth factors and their receptors and oncogenes) in regulating the growth and differentiation patterns in early embryos including trophectoderm and inner cell mass will be studied. The role of protein phosphorylation in regulating the transcriptional activity of the embryonic gene will be examined. 5) Establishment of cell lineages and the cell lineage specific gene expression will be explored by injection of suitable DNA markers and by in situ hybridization with specific probes. 6) Differentiation of trophectoderm, trophoblast and inner cell mass will be studied by identifying genes and gene products specific for those tissues, by determining their role and by attempting to specifically alter or abolish this first differentiation event in mouse embryogenesis. In view of the accessibility of trophectoderm tissue, the readily characterized sequence of developmental events involved in trophectoderm formation.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Program Projects (P01)
Project #
5P01HD021355-03
Application #
2198241
Study Section
Population Research Committee (HDPR)
Project Start
1988-06-01
Project End
1993-05-31
Budget Start
1990-06-01
Budget End
1991-05-31
Support Year
3
Fiscal Year
1990
Total Cost
Indirect Cost
Name
Wistar Institute
Department
Type
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
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Barnes, G L; Alexander, P G; Hsu, C W et al. (1997) Cloning and characterization of chicken Paraxis: a regulator of paraxial mesoderm development and somite formation. Dev Biol 189:95-111
Barnes, G L; Hsu, C W; Mariani, B D et al. (1996) Chicken Pax-1 gene: structure and expression during embryonic somite development. Differentiation 61:13-23
Barnes Jr, G L; Mariani, B D; Tuan, R S (1996) Valproic acid-induced somite teratogenesis in the chick embryo: relationship with Pax-1 gene expression. Teratology 54:93-102
Jacenko, O; San Antonio, J D; Tuan, R S (1995) Chondrogenic potential of chick embryonic calvaria: II. Matrix calcium may repress cartilage differentiation. Dev Dyn 202:27-41
Jacenko, O; Tuan, R S (1995) Chondrogenic potential of chick embryonic calvaria: I. Low calcium permits cartilage differentiation. Dev Dyn 202:13-26
Latham, K E; Garrels, J I; Solter, D (1994) Alterations in protein synthesis following transplantation of mouse 8-cell stage nuclei to enucleated 1-cell embryos. Dev Biol 163:341-50
Temeles, G L; Ram, P T; Rothstein, J L et al. (1994) Expression patterns of novel genes during mouse preimplantation embryogenesis. Mol Reprod Dev 37:121-9
Ekanayake, S; Tuan, R S (1994) Chondrogenesis of neural crest cells: effect of poly-L-lysine and bone extract. Differentiation 58:19-27
Johnson, S E; Rothstein, J L; Knowles, B B (1994) Expression of epidermal growth factor family gene members in early mouse development. Dev Dyn 201:216-26

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