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

Abstract

Cdx gene products regulate the extent of axial elongation from the posterior growth zone. These transcription factors sustain the emergence of trunk and tail tissues by providing a suitable niche in the axial progenitor zone, via regulation of Wnt signaling. Cdx genes are expressed in and along the complete primitive streak including its posterior part wherefrom the extraembryonic mesoderm of the allantois emerges. Cdx genes are required for the full development of the allantois and its derivatives in the placental labyrinth. The mouse germ cell lineage also originates from the proximo-posterior epiblast of the primitive streak, and is established within the extraembryonic mesoderm that generates the allantois. We asked whether the expression of Cdx genes around the newly specified PGCs is necessary for the maintenance and expansion of this population, as it is for the allantois and axial progenitors. We observed a significantly lower number of PGCs in Cdx2(null) embryos than in controls. We found that Wnt3a loss of function decreases the PGC population to the same extent as Cdx2 inactivation. Moreover, exogenous Wnt3a corrects the lower PGC number in Cdx2(null) posterior embryonic tissues cultured in vitro. Cdx2 is not expressed in PGCs themselves, and we propose that the expression of Cdx2 in posterior extraembryonic tissues contributes to the proper niche of the germ cell progenitors by stimulating canonical Wnt signaling. Since PGC residence within the posterior growth zone is a mouse-specific feature, our data suggest that mouse PGCs opportunistically became dependent on the axial progenitor niche.

Wnt/β-catenin signaling pathway activation is required for proliferation of chicken primordial germ cells in vitro

“…β-catenin is a key mediator of canonical Wnt signaling, and acts as a transcriptional co-activator to control the expression of cell cycle-related genes 13 14 . The importance of Wnt/β-catenin signaling in the proliferation of PGCs has been reported in mice and Drosophila 8 15 16 , but not in chickens.…”

Does murine spermatogenesis require WNT signalling? A lesson from Gpr177 conditional knockout mouse models

“…During the embryonic stage of mouse development, WNT3 and WNT3A regulate primordial germ cell (PGC) specification and early expansion. 17, 18 WNT5A-ROR2 serves as an important cue for PGC migration; loss of Wnt5a disrupts PGC migration into the genital ridge. 19, 20 It is also well established that WNT signalling mainly plays a negative role in testis determination and proper repression of WNT signalling by the SRY/SOX9/FGF9 pathway is important for normal sexual differentiation.…”

Mouse Primordial Germ Cells

“…b Because Cdx2-null mutants die prior to gastrulation due to defects in trophoblast development(Chawengsaksophak et al, 2004), analysis of PGCs, anteroposterior axis, hindgut, and allantois occurred in tetraploid-rescued mutants with wild-type trophectoderm and Cdx2-null inner cell mass, which contributes to future epiblast,(Chawengsaksophak et al, 2004) or in Sox2-Cre transgenic mice that conditionally knock out Cdx2 in the epiblast only(Bialecka et al, 2012). Abbreviations: Al, allantois; A-P, anteroposterior; AP, alkaline phosphatase; EB, early (allantoic) bud; HF, headfold; Hg, hindgut; IF, immunofluorescence; LB, late (allantoic) bud; LS, late streak; NP, neural plate; OB, no (allantoic) bud; s, somites.…”