The genetic control of early postimplantation development: An embryological and molecular analysis.

摘要

The albino-deletion complex located on chromosome 7 of the mouse represents a model system for the study of mammalian embryonic, neonatal and adult development. This series of 37 overlapping deficiencies that surround and include the albino coat color locus, when homozygous, are associated with specific developmental abnormalities. Nine genetic units have been defined by complementation analyses. These studies reveal the location of gene products needed during preimplantation, early postimplantation, perinatal and juvenile stages of development, formation of the ear labyrinth, and growth and differentiation of the embryonic ectoderm and extraembryonic ectoderm. Also included within this area of chromosome 7 is the albino locus and the structural gene for mitochondrial malic enzyme.;Embryological examination of the lethal phenotype associated with the deletion chromosomes of the original Bi complementation group defined two new complementation groups, Bex and Bem. Embryos homozygous for these deletions die between day 7.5-8.5 of gestation. These deficiencies reveal the presence of two functional units within this region of the genome that are needed during early postimplantation stages of development, one for proliferation of the embryonic ectoderm and the other for extraembryonic ectoderm formation. The extraembryonic ectoderm in deletion mutants of the Bem complementation group appears to differentiate normally. Although mesoderm is produced, neither the notochord, neural tube nor somites form and morphogenesis does not take place. Embryos homozygous for the Bex deletion chromosomes have marked abnormalities of both the extraembryonic ectoderm and embryonic ectoderm.;A molecular-genetic analysis of the region of the genome removed by the albino deletions was undertaken by generation of a partial library obtained by microdissection of mouse chromosome 7 and cloning of the DNA fragments. The microclones were localized within the deletion complex by Southern analysis of the DNA hybridization pattern produced by Mus spretus/ M. musculus interspecies cross and homozygous and double heterozygous deletion mice. Two genomic clones distinguish proximal deletion chromosome breakpoint differences within the Bem and Bex complementation groups, a distinction which was not possible genetically. These molecular markers define the limits for the Bem and Bex proximal breakpoints, establish the distal boundary associated with the perinatal survival functional region and provide a molecular starting point to enter the region of the genome needed for development of the embryonic ectoderm and extraembryonic ectoderm.