Cdx mutant axial progenitor cells are rescued by grafting to a wild type environment.
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.
Bialecka
Monika
M
Hubrecht Institute, Developmental Biology and Stem Cell Research, and Utrecht University Medical Center, Utrecht, The Netherlands.
Wilson
Valerie
V
Deschamps
Jacqueline
J
D000818:Animals; D019521:Body Patterning / Q000235:genetics; D000071616:CDX2 Transcription Factor; D049109:Cell Proliferation; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D049452:Green Fluorescent Proteins / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D008648:Mesoderm / Q000166:cytology / Q000196:embryology; D051379:Mice; D009154:Mutation / Q000235:genetics*; D054240:Primitive Streak / Q000166:cytology / Q000378:metabolism / Q000637:transplantation*; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
D000071616:CDX2 Transcription Factor; C487514:Cdx2 protein, mouse; C084563:Cdx4 protein, mouse; D018398:Homeodomain Proteins; D014157:Transcription Factors; D051176:beta Catenin; D049452:Green Fluorescent Proteins