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Abnormal migration behavior linked to Rac1 signaling contributes to primordial germ cell exhaustion in Fanconi anemia pathway-deficient Fancg −/− embryos

Abstract : Abstract Fanconi anemia (FA) is a rare human genetic disorder characterized by bone marrow failure, predisposition to cancer and developmental defects including hypogonadism. Reproductive defects leading to germ cell aplasia are the most consistent phenotypes seen in FA mouse models. We examined the role of the nuclear FA core complex gene Fancg in the development of primordial germ cells (PGCs), the embryonic precursors of adult gametes, during fetal development. PGC maintenance was severely impaired in Fancg−/− embryos. We observed a defect in the number of PGCs starting at E9.5 and a strong attrition at E11.5 and E13.5. Remarkably, we observed a mosaic pattern reflecting a portion of testicular cords devoid of PGCs in E13.5 fetal gonads. Our in vitro and in vivo data highlight a potential role of Fancg in the proliferation and in the intrinsic cell motility abilities of PGCs. The random migratory process is abnormally activated in Fancg−/− PGCs, altering the migration of cells. Increased cell death and PGC attrition observed in E11.5 Fancg−/− embryos are features consistent with delayed migration of PGCs along the migratory pathway to the genital ridges. Moreover, we show that an inhibitor of RAC1 mitigates the abnormal migratory pattern observed in Fancg−/− PGCs.
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https://hal-cnrs.archives-ouvertes.fr/hal-03376710
Contributor : Filippo Rosselli Connect in order to contact the contributor
Submitted on : Wednesday, October 20, 2021 - 11:13:25 AM
Last modification on : Wednesday, October 20, 2021 - 2:55:16 PM

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Amandine Jarysta, Lydia Riou, Virginie Firlej, Clémentine Lapoujade, Thierry Kortulewski, et al.. Abnormal migration behavior linked to Rac1 signaling contributes to primordial germ cell exhaustion in Fanconi anemia pathway-deficient Fancg −/− embryos. Human Molecular Genetics, Oxford University Press (OUP), 2021, ⟨10.1093/hmg/ddab222⟩. ⟨hal-03376710⟩

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