ADP-ribosylation factor 1 regulates asymmetric cell division in female meiosis in the mouse.
Mouse oocytes undergo two successive meiotic divisions to generate one large egg with two small polar bodies. The divisions are essential for preserving the maternal resources to support embryonic development. Although previous studies have shown that some small guanosine triphosphatases, such as RAC, RAN, and CDC42, play important roles in cortical polarization and spindle pole anchoring, no oocytes undergo cytokinesis when the mutant forms of these genes are expressed in mouse oocytes. Here, we show that the ADP-ribosylation factor 1 (ARF1) plays an important role in regulating asymmetric cell division in mouse oocyte meiosis. Microinjection of mRNA of a dominant negative mutant form of Arf1 (Arf1(T31N)) into fully grown germinal vesicle oocytes led to symmetric cell division in meiosis I, generating two metaphase II (MII) oocytes of equal size. Subsequently, the two MII oocytes of equal size underwent the second round of symmetric cell division to generate a four-cell embryo (zygote) when activated parthenogenetically or via sperm injection. Furthermore, inactivation of mitogen-activated protein kinase (MAPK) but not MDK (also known as MEK) has been discovered in the ARF1 mutant oocytes, and this further demonstrated that ARF1, MAPK pathway plays an important role in regulating asymmetric cell division in meiosis I. Similarly, ARF1(T31N)-expressing, superovulated MII oocytes underwent symmetric cell division in meiosis II when activation was performed. Rotation of the MII spindle for 90 degrees was prohibited in ARF1(T31N)-expressing MII oocytes. Taken together, our results suggest that ARF1 plays an essential role in regulating asymmetric cell division in female meiosis.
Wang
Shufang
S
National Institute of Biological Sciences (NIBS), College of Life Science, Beijing Normal University, Beijing, People's Republic of China.
Hu
Jianjun
J
Guo
Xinzheng
X
Liu
Johne X
JX
Gao
Shaorong
S
D020823:ADP-Ribosylation Factor 1 / Q000235:genetics / Q000378:metabolism*; D000089982:ADP-Ribosylation Factor 6; D020727:ADP-Ribosylation Factors / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002455:Cell Division / Q000502:physiology*; D005260:Female; D008540:Meiosis / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D009865:Oocytes / Q000166:cytology / Q000378:metabolism*; D017231:Proto-Oncogene Proteins c-mos / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
D000089982:ADP-Ribosylation Factor 6; D017231:Proto-Oncogene Proteins c-mos; D020929:Mitogen-Activated Protein Kinase Kinases; D020823:ADP-Ribosylation Factor 1; D020727:ADP-Ribosylation Factors; C541432:Arf3 protein, mouse