The maternal factor Nanog promotes a novel mechanism of fish oogenesis and egg quality through translational control

Gamete quality, especially egg quality (ooplasm), is a prerequisite
for determining fish breeding success and farming efficiency.
The egg quality of a fish is determined
by the collection of all maternal factors stored in the egg.
Research on the regulation of maternal factors on egg genesis and early embryonic development can guide the assessment of fish egg quality, improve egg quality, and promote the development of
aquatic seed industry and aquaculture industry.
In the process of egg development and maturation, a large amount of maternal mRNA is transcribed and hoarded in the egg, and its orderly translation activation or translation inhibition in time and space, that is, translational control, determines the process of egg genesis and egg quality, and even the early development
of the fertilized embryo.
Available data suggest that maternal mRNA requires tight translation control
during egg development.
Mechanisms of maternal mRNA translation control have been reported by regulating the length of the mRNA's poly(A) or by specific RNA-binding protein sequence-specific inhibition of the translation of certain mRNA
.
 

On December 19, the research paper entitled "Maternal Nanog Promotes Egg Genesis and Embryonic Development through Translation Control" in the international academic journal Development published a research article entitled "Maternal Nanog Promotes Egg Genesis and Embryonic Development through Translation Control", using zebrafish as a model to reveal a new mechanism
by which maternal factor Nanog promotes egg quality by regulating the translation control of maternal mRNA at the global level 。 This article was selected by the editor-in-chief as the research highlight of the issue, and a review article entitled "Nanog, not only a pluripotency factor" was highlighted and recommended
.

Figure 1 The current issue of the journal distributed a review entitled "Nanog, not only a pluripotency factor", and highlighted the papers of Sun Yonghua's team

In the previous study, the team used the zebrafish model to construct a loss-of-function mutant of the important maternal factor Nanog through TALENs technology (He et al.
, Mutation Research, 2015), and elucidated a new mechanism by which the binding of maternal Nanog to TCF factors inhibits the global activation of maternal β-catenin signaling and thus protects early embryonic development (He, et al.
, 2020, PLOS Biology).

。 However, as an important maternal gene that begins to be expressed during oogenesis (Figure 2A), the regulatory role of Nanog in the process of oogenesis remains unknown
.
By analyzing the phenotype of the nanog maternal mutant, the team found that the deletion of the maternal nanog led to severe sterilization of early embryos, with severe defects in the mutant's egg maturation (Figure 2).

Fig.
2 Loss of maternal nanog leads to defects in egg maturation and early embryonic development  

Further proteome and transcriptome studies found that the level of translation in mutant eggs was significantly upregulated and the transcription level of the translation eef1a1l2 was significantly increased
.
By knocking out EEF1A1L2 in the nanog mutant, the translation activity in the eggs of the double mutant was significantly downregulated, and the egg maturation defects were significantly improved.
What's more, defects in early embryonic development have also been significantly rescued (Figure 3).

Figure 3 Co-knockout of EEF1A1L2 can save OEG mutants from ozoogenesis and early embryonic development defects

Through the above research, the team discovered a new mechanism for regulating oogenesis and early embryonic development by maternal factor Nanog through translation control of maternal mRNA (Figure 4): in wild-type eggs, Nanog inhibits its transcription by binding to the promoter of the translation eef1a1l2 to ensure that the translational activity in the egg is at a normal level, and the resulting eggs can be fertilized normally and guide early embryonic development; In nanog mutants, due to the deletion of Nanog's transcriptional inhibition of eef1a1l2, eef1a1l2 abnormally activates transcription in eggs, resulting in abnormal activation of the translation machine for oogenesis, excessive protein accumulation leads to poor egg quality, and eventually leads to developmental defects in the embryo after fertilization; After the co-knockout of EEF1A1L2, the translation machine in the double-mutant egg returned to normal levels, the protein expression overload was alleviated, the egg quality was significantly improved, and the defects in early embryonic development were significantly rescued
.
Thus, the study reveals that Nanog acts as a transcriptional suppressor to inhibit the transcription of translation eef1a1l2 during oogenesis, thereby providing translational control over the ovigenesis process at a global level, promoting ovogenesis and early embryonic development
.

Figure 4 Molecular model of Nanog regulating oogenesis and early embryonic development via EEF1A1L2

It is worth mentioning that contrary to the discovery by many scholars that Nanog plays the role of transcriptional activator during zygotic gene activation (Lee et al.
, Nature 2013; Veil et al.
, Genome Research 2019; Pálfy et al.
, PLOS Genetics 2020; Miao et al.
, Molecular Cell 2022), which found that Nanog plays the role of transcriptional repressor during oogenesis, suggesting that Nanog as a pioneer factor completes the role switch from a transcriptional suppressor to a transcriptional activator during ovulogenesis and embryonic development
。

Associate researcher and doctoral student Jiao Shengbo of the He Peony Project of the Institute of Aquatic Sciences are the co-first authors of the paper, researcher Sun Yonghua is the corresponding author, and Dr.
Zhang Ru, associate researcher Ye Ding and experimental scientist Wang Houpeng participated in the work
.
This research was supported
by the National Science Foundation for Outstanding Young Scholars and the National Natural Science Foundation of China.
The mutants produced in this paper have been preserved in the National Zebrafish Resource Center
, the National Aquatic Germplasm Resource Bank.

Article link: https://doi.
org/10.
1242/dev.
201213

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