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XB-ART-44949
Development April 1, 2012; 139 (8): 1476-86.

Xenopus Nanos1 is required to prevent endoderm gene expression and apoptosis in primordial germ cells.

Lai F , Singh A , King ML .


Abstract
Nanos is expressed in multipotent cells, stem cells and primordial germ cells (PGCs) of organisms as diverse as jellyfish and humans. It functions together with Pumilio to translationally repress targeted mRNAs. Here we show by loss-of-function experiments that Xenopus Nanos1 is required to preserve PGC fate. Morpholino knockdown of maternal Nanos1 resulted in a striking decrease in PGCs and a loss of germ cells from the gonads. Lineage tracing and TUNEL staining reveal that Nanos1-deficient PGCs fail to migrate out of the endoderm. They appear to undergo apoptosis rather than convert to normal endoderm. Whereas normal PGCs do not become transcriptionally active until neurula, Nanos1-depleted PGCs prematurely exhibit a hyperphosphorylated RNA polymerase II C-terminal domain at the midblastula transition. Furthermore, they inappropriately express somatic genes characteristic of endoderm regulated by maternal VegT, including Xsox17α, Bix4, Mixer, GATA4 and Edd. We further demonstrate that Pumilio specifically binds VegT RNA in vitro and represses, along with Nanos1, VegT translation within PGCs. Repressed VegT RNA in wild-type PGCs is significantly less stable than VegT in Nanos1-depleted PGCs. Our data indicate that maternal VegT RNA is an authentic target of Nanos1/Pumilio translational repression. We propose that Nanos1 functions to translationally repress RNAs that normally specify endoderm and promote apoptosis, thus preserving the germline.

PubMed ID: 22399685
PMC ID: PMC3308181
Article link: Development
Grant support: [+]
Genes referenced: a2m bix1.3 ctrl ddx25 gata4 mixer mmut muc1 nanos1 odc1 pgat pgc piwil1 polr2a pum1 sox17a tbxt vegt
Antibodies: Nanos1 Ab1 Polr2a Ab1
Morpholinos: nanos1 MO1


Article Images: [+] show captions
References:
Ahringer, 1991, Pubmed [+]


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