Cdx mutant axial progenitor cells are rescued by grafting to a wild type environment

Abstract

Cdx transcription factors are required for axial extension. Cdx genes are expressed in the posterior growth zone, a region that supplies new cells for axial elongation. Cdx2(+/-)Cdx4(-/-) (Cdx2/4) mutant embryos show abnormalities in axis elongation from E8.5, culminating in axial truncation at E10.5. These data raised the possibility that the long-term axial progenitors of Cdx mutants are intrinsically impaired in their ability to contribute to posterior growth. We investigated whether we could identify cell-autonomous defects of the axial progenitor cells by grafting mutant cells into a wild type growth zone environment. We compared the contribution of GFP labeled mutant and wild type progenitors grafted to unlabeled wild type recipients subsequently cultured over the period during which Cdx2/4 defects emerge. Descendants of grafted cells were scored for their contribution to differentiated tissues in the elongating axis and to the posterior growth zone. No difference between the contribution of descendants from wild type and mutant grafted progenitors was detected, indicating that rescue of the Cdx mutant progenitors by the wild type recipient growth zone is provided non-cell autonomously. Recently, we showed that premature axial termination of Cdx mutants can be partly rescued by stimulating canonical Wnt signaling in the posterior growth zone. Taken together with the data shown here, this suggests that Cdx genes function to maintain a signaling-dependent niche for the posterior axial progenitors.

Evolutionarily conserved requirement of Cdx for post-occipital tissue emergence

“…Embryos were cultured for 48 hours as described by Bialecka et al (Bialecka et al, 2010). Each experiment contained control and Cdx mutant embryos with and without Fgf8.…”

“…Genetic analysis revealed that the axial extension defects of these mutants could be rescued by either a gain-of-function of Hox genes belonging to the middle part of the Hox clusters, or by expressing an activated form of the Wnt signaling effector Lef1 in the spatiotemporal window of Cdx expression (Young et al, 2009). The latter information and subsequent grafting experiments of the region harboring stem celllike axial progenitors for trunk and tail tissues from Cdx2/4 mutants into wild-type recipients revealed that the Cdx mutations disable the surrounding niche of these progenitors rather than the progenitors themselves (Bialecka et al, 2010). So far, the impact of ablating all three Cdx genes had not been tested.…”

Cdx2 contributes to the expansion of the early primordial germ cell population in the mouse

“…They are therefore presumed to affect the axial progenitor population present between the node and the most anterior part of the primitive streak, which was shown by Wilson (2002, 2007) to deliver somitic mesoderm and neurectoderm descendants to the elongating axis. Grafting this population from a Cdx mutant embryo orthotopically to a wild type recipient rescues their contribution to mesoderm and neurectoderm that was impaired by the Cdx deficiency (Bialecka et al, 2010). Cdx mutations thus affect the environment of the axial progenitors rather than the self-renewal and differentiation potential of these progenitors themselves.…”

Control of Hes7 Expression by Tbx6, the Wnt Pathway and the Chemical Gsk3 Inhibitor LiCl in the Mouse Segmentation Clock

“…Finally, the X-gal staining of the PSM was lost in the H7p1.0dR reporter, demonstrating that this 400 bp Hes7 promoter region is important for Hes7 promoter activity (Figure 1). This 400 bp region is strongly conserved in humans and contains binding sites for interesting transcription factors such as Lef1 (Wnt pathway effector) [17], Ets (Fgf pathway effector) [18], the mesodermal factor Tbx6 [19], and the axial elongation factor Cdx2 [20] (Figure S1). …”