Translational inhibition of cyclin B1 and appearance of cyclin D1 very early in the differentiation of mouse trophoblast giant cells.
Investigation of the basis of uncoupling of replication of the genome from mitosis in the mouse trophoblast has so far been neglected despite its significance for understanding both placental development and cell cycle control. In order to obtain clues about the molecular basis of the switch from proliferation to endoreduplication, we have investigated changes in the expression of cyclins and cyclin-dependent kinases in diploid versus giant trophoblast cells. Interestingly, while cyclin B1 transcripts were found in both diploid and giant cells, the protein was found exclusively in diploid cells. This could be explained by either inhibition of translation or by constitutive degradation of the protein. The latter was ruled out by examining blastocysts which had been cultured in the presence of the proteasome inhibitor N-acetyl-leu-leu-norleucinal followed by immunostaining for cyclin B1. In these experiments cyclin B1 protein accumulated in diploid but not in giant cells. Fusion of trophoblast giant cells with secondary oocytes, which are rich in maturation promoting factor (MPF) activity, revealed that an exogenous source of active MPF could cause chromosome condensation and nuclear envelope breakdown in endocycling cells; therefore endoreduplication via polyteny evidently requires the suppression of MPF activity. In addition, cyclin D1 transcripts were found only in giant cells and, interestingly, the beginning of its expression was evident prior to that of placental lactogen I, an early marker of trophoblast differentiation. The results suggest that supression of MPF activity, by inhibition of translation of cyclin B1, is a key mechanism for the establishment of the endocycle in the mouse trophoblast.
Palazón
L S
LS
Department of Zoology, University of Oxford, UK.
Davies
T J
TJ
Gardner
R L
RL
D000818:Animals; D002453:Cell Cycle / Q000502:physiology*; D002454:Cell Differentiation; D019926:Cyclin B / Q000096:biosynthesis* / Q000235:genetics; D056744:Cyclin B1; D019938:Cyclin D1 / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D015726:Giant Cells / Q000502:physiology; D000090204:Mesothelin; D051379:Mice; D011123:Polyploidy; D011247:Pregnancy; D014327:Trophoblasts / Q000166:cytology / Q000502:physiology*
C534700:Ccnb1 protein, mouse; D019926:Cyclin B; D056744:Cyclin B1; C000715528:Msln protein, mouse; D019938:Cyclin D1; D000090204:Mesothelin