Regulation of early embryo development: functional redundancy between cyclin subtypes

2001 ◽  
Vol 13 (1) ◽  
pp. 59 ◽  
Author(s):  
Nicola Winston ◽  
Nicola Winston

Cellular proliferation during early embryo development is achieved by the serial cleavage of individual blastomeres into increasingly smaller cells, in the absence of cell growth. This simplified cell division process has facilitated the study of the cell cycle and its regulatory pathways. The cell cycle of mammalian cells is controlled by a number of mechanisms, including the activity of cyclin-dependent protein kinase complexes. Numerous cyclin proteins have been identified and these share structural and functional characteristics. For each of the A- and B-type cyclins, two subtypes have been identified so far in mammals. However, in both cases the two subtype genes are expressed differentially, suggesting that they might have specific roles. The requirement for individual cyclin A and B proteins during early mouse embryo development has been examined using gene-targeted deletion and immunofluorescence techniques. These studies have shown that cyclin A1 is not essential for early embryonic development and cyclin A2 only becomes essential for development beyond the stage of implantation. Cyclin B1 is also essential for development and its critical regulatory role during the meiotic maturation of mouse oocytes will be considered. This review will discuss the studies that have attempted to explain the possible redundancy between the different cyclin subtypes.

2009 ◽  
Vol 21 (1) ◽  
pp. 112
Author(s):  
I. Choi ◽  
K. H. S. Campbell

After fertilization, early embryo development is dependent upon maternally inherited proteins and protein synthesised from maternal mRNA until zygotic gene activation (ZGA) occurs. The transition of transcriptional activity from maternal to embryonic control occurs with the activation of rRNA genes and the formation of the nucleolus at the 8- to 16-cell stage that coincides with a prolonged fourth cell cycle in bovine and ovine embryos. However, previous studies have reported a shift in the longest cell cycle (fifth cell cycle) in bovine somatic cell nuclear transfer (SCNT) embryos, suggesting that the major genome activation is delayed, possibly due to incomplete changes in chromatin structure such as hypermethylation and hypoacetylation of histone (Memili and First 2000 Zygote 8, 87–96; Holm et al. 2003 Cloning Stem Cells 5, 133–142). Although global gene expression profile studies have been carried out in somatic cell nuclear transfer embryos, little is known about the expression of genes which can alter chromatin structure in early embryo development and possibly effect ZGA. To determine whether epigenetic reprogramming of donor nuclei affected ZGA and expression profiles in SCNT embryos, ZBTB33 (zinc finger and BTB domain containing 33, also known as kaiso, a methy-CpG specific repressor), BRG1(brahma-related gene 1, SWI/SNF family of the ATP-dependent chromatin remodeling complexes), JMJD1A (jumonji domain containing 1A, H3K9me2/1-specific demethylase), JMJD1C (putative H3K9-specific demethylase), and JMJD2C (H3K9me3-specific demethylase) were examined by RT-PCR at different developmental stages [germinal vesicle (GV), metaphase II (MII), 8- to 16-cell, 16- to 32-cell, and blastocyst in both parthenogenetic and SCNT embryos]. All genes were detected in parthenogenetic and SCNT blastocyts, and ZBTB33 was also expressed in all embryos at all stages tested. However, the onset of expression of JMJD1C, containing POU5F1 binding site at 5′-promoter region and BRG1 required for ZGA are delayed in SCNT embryos as compared to parthenotes (16- v. 8-cell, and blastoocyst v. 16-cell stage). Furthermore, JMJD2C containing NANOG binding sites at the 3′-flanking region was expressed in GV and MII oocytes and parthenogenetic blastocysts, whereas in SCNT embryos, JMJD2C was only observed from the 16-cell stage onwards. Interestingly, JMJD1A, which is positively regulated by POU5F1, was not detected in GV and MII oocytes but was present in blastocyst stage embryos of both groups. Taken together, these results suggest that incomplete epigenetic modifications of genomic DNA and histones lead to a delayed onset of ZGA which may affect further development and establishment of totipotency. Subsequently, aberrant expression patterns reported previously in SCNT embryos may be attributed to improper expression of histone H3K9 and H3K4 demethylase genes during early embryo development.


2009 ◽  
Vol 21 (6) ◽  
pp. 805 ◽  
Author(s):  
Ngoc Tan Nguyen ◽  
David Pei-Cheng Lin ◽  
Shih-Ying Yen ◽  
Jung-Kai Tseng ◽  
Jui-Fen Chuang ◽  
...  

In the present study, we investigated the effects of the Sonic hedgehog (Shh) protein on porcine oocyte maturation and early embryo development. Immunohistochemistry showed activation of Shh signalling in cumulus–oocyte complexes (COCs), as reflected by Patched (Ptc), Smoothened (Smo) and Gli1 expression in oocytes, cumulus cells and granulosa cells, particularly those of small follicles (<2 mm in diameter). Western blot analysis showed Smo expression in COCs and in denuded oocytes derived from small and medium (3–7 mm)-sized follicles. Small follicles contained the highest concentration of Shh in follicular fluid compared with medium-sized and large (>7 mm in diameter) follicles. Supplementation with Shh (0.5 or 1 μg mL–1) enhanced oocyte maturation compared with the control group (92.4% and 90.4% v. 81.9%, respectively; P < 0.05). This effect was reversed by the simultaneous addition of cyclopamine (1–2 μm), an Shh inhibitor. Similar to intact COCs, denuded COCs showed enhanced maturation following Shh supplementation. Furthermore, cyclin B1 content, extracellular signal-regulated kinase 1/2 phosphorylation, intracellular calcium release, blastocyst rate and total cell numbers were greater (P < 0.05) in oocytes matured in the presence of 0.5 and 1 μg mL–1 Shh compared with control oocytes. The findings of the present study provide the first evidence that the Shh signalling pathway is active, or at least partially activated, in the porcine ovary and is likely to promote oocyte cytoplasmic and nuclear maturation, as well as subsequent in vitro development, although the underlying mechanisms remain to be elucidated.


2014 ◽  
Vol 37 (2) ◽  
pp. 126-132 ◽  
Author(s):  
Xiao-Xin Dai ◽  
Xing Duan ◽  
Hong-Lin Liu ◽  
Xiang-Shun Cui ◽  
Nam-Hyung Kim ◽  
...  

2019 ◽  
Author(s):  
Isabel G&oacute;mez-Redondo ◽  
Priscila Ramos-Ibeas ◽  
Eva Pericuesta ◽  
Benjamín Planells ◽  
Raul Fernández-González ◽  
...  

2021 ◽  
Author(s):  
Zhen Sun ◽  
Hua Yu ◽  
Jing Zhao ◽  
Tianyu Tan ◽  
Hongru Pan ◽  
...  

AbstractLIN28 is an RNA binding protein with important roles in early embryo development, stem cell differentiation/reprogramming, tumorigenesis and metabolism. Previous studies have focused mainly on its role in the cytosol where it interacts with Let-7 microRNA precursors or mRNAs, and few have addressed LIN28’s role within the nucleus. Here, we show that LIN28 displays dynamic temporal and spatial expression during murine embryo development. Maternal LIN28 expression drops upon exit from the 2-cell stage, and zygotic LIN28 protein is induced at the forming nucleolus during 4-cell to blastocyst stage development, to become dominantly expressed in the cytosol after implantation. In cultured pluripotent stem cells (PSCs), loss of LIN28 led to nucleolar stress and activation of a 2-cell/4-cell-like transcriptional program characterized by the expression of endogenous retrovirus genes. Mechanistically, LIN28 binds to small nucleolar RNAs and rRNA to maintain nucleolar integrity, and its loss leads to nucleolar phase separation defects, ribosomal stress and activation of P53 which in turn binds to and activates 2C transcription factor Dux. LIN28 also resides in a complex containing the nucleolar factor Nucleolin (NCL) and the transcriptional repressor TRIM28, and LIN28 loss leads to reduced occupancy of the NCL/TRIM28 complex on the Dux and rDNA loci, and thus de-repressed Dux and reduced rRNA expression. Lin28 knockout cells with nucleolar stress are more likely to assume a slowly cycling, translationally inert and anabolically inactive state, which is a part of previously unappreciated 2C-like transcriptional program. These findings elucidate novel roles for nucleolar LIN28 in PSCs, and a new mechanism linking 2C program and nucleolar functions in PSCs and early embryo development.


2016 ◽  
Vol 27 (5) ◽  
pp. 768-775 ◽  
Author(s):  
Xue-Shan Ma ◽  
Fei Lin ◽  
Zhong-Wei Wang ◽  
Meng-Wen Hu ◽  
Lin Huang ◽  
...  

Geminin controls proper centrosome duplication, cell division, and differentiation. We investigated the function of geminin in oogenesis, fertilization, and early embryo development by deleting the geminin gene in oocytes from the primordial follicle stage. Oocyte-specific disruption of geminin results in low fertility in mice. Even though there was no evident anomaly of oogenesis, oocyte meiotic maturation, natural ovulation, or fertilization, early embryo development and implantation were impaired. The fertilized eggs derived from mutant mice showed developmental delay, and many were blocked at the late zygote stage. Cdt1 protein was decreased, whereas Chk1 and H2AX phosphorylation was increased, in fertilized eggs after geminin depletion. Our results suggest that disruption of maternal geminin may decrease Cdt1 expression and cause DNA rereplication, which then activates the cell cycle checkpoint and DNA damage repair and thus impairs early embryo development.


PLoS ONE ◽  
2016 ◽  
Vol 11 (9) ◽  
pp. e0162272 ◽  
Author(s):  
Wei Zhao ◽  
Feng Yao ◽  
Mengchen Zhang ◽  
Ting Jing ◽  
Shuang Zhang ◽  
...  

Author(s):  
Xavier Ferraretto ◽  
Karima Hammas ◽  
Marie-Astrid Llabador ◽  
Solenne Gricourt ◽  
Julie Labrosse ◽  
...  

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