Morphogenesis duringXenopusgastrulation requires Wee1-mediated inhibition of cell proliferation

Abstract

the induction of zygotic transcription. In addition, Wee1 is positively regulated by tyrosine autophosphorylation in early gastrula embryos and this upregulation of Wee1 activity is required for normal gastrulation. We also show that overexpression of Cdc25C, a phosphatase that activates the CyclinB/Cdc2 complex, induces gastrulation defects that can be rescued by Wee1, providing additional evidence that cell cycle inhibition is crucial for the gastrulation process. Together, these findings further elucidate the developmental function of Wee1 and demonstrate the importance of cell cycle regulation in vertebrate morphogenesis.

Developmental roles of tribbles protein family members

“…Rapid embryonic cell divisions are slowed at the Xenopus mid-blastula transition (MBT), likely because cell rounding during cytokinesis is incompatible with actin Developmental Dynamics cytoskeletal remodeling during migration (reviewed in Duncan and Su, 2004). Consistent with this finding, experimental manipulations that prevent the MBT delay, such as the injection of morpholinos that deplete maternal Wee1 or overexpression of Cdc25/string, also result in gastrulation defects (Murakami et al, 2004).…”

Cdc25 and the importance of G2control

“…[38][39][40] If Cdc25 activity is not restricted in either model system, cells that should be gastrulating continue to divide, which places too much demand on the cytoskeleton eventually leading to embryo lethality. 6,36,38,39 Gastrulating zebrafish cells induce an EMT that is actin-mediated but does not use apical constriction (Fig. 3A).…”

“…In Xenopus, this is accomplished by an increase in wee1 expression in the cells undergoing apical constriction. 36,37 In Drosophila, Tribbles causes the degradation of the Cdc25 orthologs, String and Twine. [38][39][40] If Cdc25 activity is not restricted in either model system, cells that should be gastrulating continue to divide, which places too much demand on the cytoskeleton eventually leading to embryo lethality.…”

Death-effector domain-containing protein DEDD is an inhibitor of mitotic Cdk1/cyclin B1

“…In contrast, an inadequate duration before division, due to aberrant phosphorylation of Tyr-15, causes cells to enter mitosis before sufficient growth, resulting in decreased size of the daughter cells (14-17). Interestingly, the loss of Wee1-related kinases, responsible for phosphorylation of Thr-14/Tyr-15, causes premature cell division in yeast, Xenopus, or Drosophila cells, but not in higher mammalian cells (4,5,9,10,(15)(16)(17)(18). This suggests the presence of alternative mechanism(s), which may also influence cell size, particularly in mammalian cells.…”