Twelve of these double mutants were severely shortened (compare Fig. 1 b, e, and f), and wavy aspect of the neural tube (not shown). 1 b) body turning, dilated heart cavities (C and V in Fig. In contrast, all E9.5 RXRα −/−/RXRβ −/− mutants displayed variable degrees of truncation of the caudal region, incomplete (Fig. (×50.) RXRα −/−/RXRβ −/− Embryos Are Severely Malformed.Į8.5 RXRα −/−/RXRβ −/− mutants ( n = 4) were externally indistinguishable from their littermates (data not shown). The asterisk indicates an artifactual tissue detachment generated during embedding. A, allantois C, chorionic plate D, diploid trophoblast E, ectoplacental cone EM, embryo G, giant cell zone L, labyrinthine zone S, spongiotrophoblast zone U, uterine epithelium LU, uterine lumen Y, yolk sac arrowheads and arrow point to allantoic capillaries (containing nucleated erythrocytes) and to maternal blood sinuses, respectively. ( d– f) The size of the structures contributing to the mutant placenta increases between E8.5 and E10.5, but their differentiation is arrested at E8.5 (see the main text for further details). ( c) At E10.5, the labyrinthine zone has enlarged markedly.
( b) At E9.5, the placenta consists of four regions: ( i) the chorionic plate (C), which is now traversed by allantoic capillaries (arrowheads) ( ii) the labyrinthine zone (L), which is composed of strands of diploid trophoblast cells and of a network of extraembryonic capillaries interspersed with maternal blood sinuses ( iii) the spongiotrophoblast zone (S), in which only maternal blood circulates and ( iv) the giant cell zone (G). The chorionic plate forms a solid wall of epithelial cells continuous with the ectoplacental cone and is fused to the mesoderm of the allantois (A), which contains extraembryonic blood vessels (arrowheads). It contains embryo-derived diploid and polyploid (giant) trophoblast cells (D and G, respectively), as well as maternal blood sinuses (arrows). The ectoplacental cone penetrates into the uterine epithelium (U).
( a) In E8.5 WT embryos, the polar extraembryonic ectoderm has generated the ectoplacental cone (E) and the chorionic (ectoplacental) plate (C). Thus, RXRα/RAR (α, β, and γ) heterodimers are the main functional units that transduce retinoid signals during ontogenesis.įigure 2 Comparison of histological sections through the implantation site of wild-type (WT) ( a– c) and RXRα −/−/RXRβ −/− (Xα/Xβ) mutants ( d– f). In contrast, there is no apparent synergism during development between RARs (α, β, or γ) and RXRβ or RXRγ inactivations ( 5).
Arrested development since the last time rar rar#
Moreover, compound mutants in which either a RXRα null mutation or a mutation (RXRαAF2°) deleting the last helical α structure of the RXRα ligand-binding domain (AF-2 AD core) is associated with a null mutation of one of the three RAR isotypes (α, β, or γ) altogether recapitulate most of the abnormalities exhibited by RAR/RAR compound mutants (refs. RXRα −/− fetuses die at embryonic days (E) 12.5–16.5 and display a myocardial hypoplasia, as well as conotruncal and ocular defects that have been observed in RAR/RAR compound mutants and belong to the fetal vitamin A deficiency syndrome ( 3, 4). RXR knockouts in the mouse therefore should generate defects that are also associated with null mutations of their heterodimerization partners.
0 kommentar(er)
