Support for the selective chromatid segregation hypothesis advanced for the mechanism of left-right body axis development in mice.
The somatic DNA strand-specific imprinting to effect gene regulation and selective chromatid segregation model was previously proposed to produce developmentally nonequivalent sister cells in mitosis. Such a mechanism might explain generation of stem-cell pattern of cell division in eukaryotes. The developmentally controlled process involves a pair of homologous chromosomes at a specific cell division to establish embryonic left-right body axis asymmetry. As a result, visceral organs in the two sides of vertebrate's body develop asymmetrically. The model was specifically proposed to explain the well-known axis randomization phenotype of the left-right dynein mutant mice where one-half of animals develop with standard visceral organ's positioning and the balance develops with the inverted arrangement. The model postulated that the specific dynein, a microtubule-based molecular motor protein, promotes the selective chromatid segregation process in mitosis. Thus, random segregation involving sister chromatids of a pair of specific chromosomes leads to axis randomization of the mutant. Moreover, the model uniquely predicts that 50 percent mutant embryos should produce symmetrical cell divisions because of random segregation; consequently, their either visceral side would develop as mirror image of the other side resulting in embryonic lethality. In view of this prediction, validity of prominent body axis-determination models is scrutinized here. Results supporting the cell-type regulated chromosome 6 and chromosome 7 selective chromatids segregation phenomenon existing in mouse cells are reviewed. Published results with the mutant mice are consistent with the chromosome segregation model for axis determination.
Klar
Amar J S
AJ
Gene Regulation and Chromosome Biology Laboratory, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD 21702-1201, USA. klar@ncifcrf.gov
D000818:Animals; D019521:Body Patterning / Q000502:physiology*; D002842:Chromatids / Q000502:physiology*; D020090:Chromosome Segregation; D004622:Embryo, Mammalian; D047108:Embryonic Development; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D008957:Models, Genetic