| Autor: |
Minocha S. Sung T.-L. Villeneuve D. Lammers F. and Herr W. |
| Rok vydání: |
2016 |
| Zdroj: |
Developmental Biology |
| Popis: |
Early in female mammalian embryonic development cells randomly inactivate one of the two X chromosomes to achieve overall equal inactivation of parental X linked alleles. Hcfc1 is a highly conserved X linked mouse gene that encodes HCF 1 a transcriptional co regulator implicated in cell proliferation in tissue culture cells. By generating a Cre recombinase inducible Hcfc1 knock out (Hcfc1(lox)) allele in mice we have probed the role of HCF 1 in actively proliferating embryonic cells and in cell cycle re entry of resting differentiated adult cells using a liver regeneration model. HCF 1 function is required for both extraembryonic and embryonic development. In heterozygous Hcfc1(lox/+) female embryos however embryonic epiblast specific Cre induced Hcfc1 deletion (creating an Hcfc1(epiKO) allele) around E5.5 is well tolerated; it leads to a mixture of HCF 1 positive and negative epiblast cells owing to random X chromosome inactivation of the wild type or Hcfc1(epiKO) mutant allele. At E6.5 and E7.5 both HCF 1 positive and negative epiblast cells proliferate but gradually by E8.5 HCF 1 negative cells disappear owing to cell cycle exit and apoptosis. Although generating a temporary developmental retardation the loss of HCF 1 negative cells is tolerated leading to viable heterozygous offspring with 100 skewed inactivation of the X linked Hcfc1(epiKO) allele. In resting adult liver cells the requirement for HCF 1 in cell proliferation was more evident as hepatocytes lacking HCF 1 fail to re enter the cell cycle and thus to proliferate during liver regeneration. The survival of the heterozygous Hcfc1(epiKO/+) female embryos even with half the cells genetically compromised illustrates the developmental plasticity of the post implantation mouse embryo in this instance permitting survival of females heterozygous for an X linked embryonic lethal allele. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
|
