NANOG is dispensable for hypoblast but essential for embryonic disc development during conceptus elongation in sheep
- 1INIA, CSIC
Abstract
NANOG is a conserved regulator of epiblast identity and is essential for hypoblast development and embryo survival after the blastocyst stage in mice. However, its role during post-blastocyst development remains poorly understood in non-rodent mammals. Here, we investigated the function of NANOG during ovine embryogenesis using CRISPR/Cas9-mediated gene ablation. NANOG ablation did not affect blastocyst formation or the initial development of the epiblast. However, NANOG-deficient blastocysts contained significantly fewer SOX17+ hypoblast cells by day (D) 8, followed by reduced hypoblast migration during early post-hatching stages in D12 in vitro embryos. These defects were transient, as hypoblast development was comparable between NANOG-deficient and wild-type conceptuses during subsequent in vivo conceptus elongation from embryonic day (E) 11 onwards. In contrast, although extraembryonic membranes development and conceptus elongation proceeded normally, NANOG-deficient conceptuses lacked SOX2+ epiblast cells and failed to form an embryonic disc (ED) from E11 onwards. These findings demonstrate that NANOG is dispensable for hypoblast development but is required for epiblast maintenance and ED formation during conceptus elongation in sheep.
Related
- Spinal microglia are dispensable for the development of opioid-induced hyperalgesia
- Complex I is essential for embryonic stem cell proliferation through NADH-mediated redox signaling
- A blood–CSF barrier function controls embryonic CSF protein composition and homeostasis during early CNS development
- Chlamydia muridarum TC0066 is required for invasion and intracellular development in tissue culture but dispensable in the murine infection model
- Multi-stage single-cell atlas of a chordate non-embryonic development unveils dedifferentiating bud founder cells
BibTeX
@misc{reyes2026nanog,
title = {{NANOG is dispensable for hypoblast but essential for embryonic disc development during conceptus elongation in sheep}},
author = {N. Martinez de los Reyes and M. Carvajal-Serna and P. Marigorta and A. Toledano-Diaz and J. Santiago-Moreno and P. Bermejo-Alvarez and P. Ramos-Ibeas},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.24.754098},
url = {https://www.biorxiv.org/content/10.64898/2026.09.24.754098v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - NANOG is dispensable for hypoblast but essential for embryonic disc development during conceptus elongation in sheep
AU - N. Martinez de los Reyes
AU - M. Carvajal-Serna
AU - P. Marigorta
AU - A. Toledano-Diaz
AU - J. Santiago-Moreno
AU - P. Bermejo-Alvarez
AU - P. Ramos-Ibeas
PY - 2026
DA - 2026/09/24
PB - bioRxiv
DO - 10.64898/2026.09.24.754098
UR - https://www.biorxiv.org/content/10.64898/2026.09.24.754098v1
AB - NANOG is a conserved regulator of epiblast identity and is essential for hypoblast development and embryo survival after the blastocyst stage in mice. However, its role during post-blastocyst development remains poorly understood in non-rodent mammals. Here, we investigated the function of NANOG during ovine embryogenesis using CRISPR/Cas9-mediated gene ablation. NANOG ablation did not affect blastocyst formation or the initial development of the epiblast. However, NANOG-deficient blastocysts contained significantly fewer SOX17+ hypoblast cells by day (D) 8, followed by reduced hypoblast migration during early post-hatching stages in D12 in vitro embryos. These defects were transient, as hypoblast development was comparable between NANOG-deficient and wild-type conceptuses during subsequent in vivo conceptus elongation from embryonic day (E) 11 onwards. In contrast, although extraembryonic membranes development and conceptus elongation proceeded normally, NANOG-deficient conceptuses lacked SOX2+ epiblast cells and failed to form an embryonic disc (ED) from E11 onwards. These findings demonstrate that NANOG is dispensable for hypoblast development but is required for epiblast maintenance and ED formation during conceptus elongation in sheep.
ER -