A cell cycle arrest is necessary for bottle cell formation in the early Xenopus gastrula: Integrating cell shape change, local mitotic control and mesodermal patterning

Abstract

During development cell proliferation and morphogenetic movements are tightly intermingled. Both processes depend on the same cytoskeletal elements. Therefore, precise regulation of local mitotic activity seems to be basic for proper embryogenesis. Here, I report on bottle cells as an early non-mitotic cell population in the Xenopus gastrula. Endogenous and activin/BVg1-induced ectopic bottle cells do not proliferate. Overexpression of the mitosis-promoting phosphatase cdc25C increases the proliferation rate and interferes with bottle cell formation whereas the phosphatase-dead mutant cdc25C(C457A) does not. Cdc25C also affects other gastrulation processes such as epiboly, vegetal rotation or tissue separation as inferred from histological inspection of early gastrulae. Double stainings of gsc/Xbra transcripts and mitotic nuclei in ectopic and endogenous lips demonstrated that non-mitotic cells occur in the bottle cell region and, to a lesser extent, in the gsc domain which both are indicative of high TGF-beta signalling. In contrast, the Xbra-region and the remainder of the animal cap appear to be permissive for higher rates of cell proliferation. These data suggest inhibition of cell proliferation by high levels of activin-type signals and a close link of mesodermal and mitotic patterning. Finally, coexpression of eFGF together with activin/BVg1 interferes with TGF-beta-induced bottle cell formation. This inhibitory effect correlates with increased cell proliferation as compared to embryos injected with activin/BVg1 alone. Taken together, these data suggest that TGF-beta and FGF signals play antagonistic roles in bottle cell formation and the spatial control of the cell cycle in early Xenopus gastrulae.

Xnrs and Activin Regulate Distinct Genes during Xenopus Development: Activin Regulates Cell Division

“…Similarly, in a control embryo stained as a whole-mount and then sectioned, the mitotic index was 0%; in an embryo injected with MO3 it was 20%. This failure of the dorsal axial mesoderm to undergo cell cycle arrest is consistent with the observed mis-regulation of cell cycle genes, and it may explain why embryos lacking activin function fail to gastrulate properly [see refs 20]–[22].…”

“…It further proved that the nodal-related proteins often regulate the expression of genes involved in regional specification, while activin particularly regulates genes involved in the control of the cell cycle. Consistent with this observation, we find that inhibition of activin B in the early embryo causes dorsal axial mesodermal cells to fail to exit the cell cycle: the results of others [20]–[22] suggest that it is the continued proliferation of these cells that underlies the gastrulation defects observed in such embryos.…”

“…One of the effects of the loss of activin B function is a disruption of gastrulation [3], and in this connection we note that the mitotic index of involuting dorsal mesoderm is significantly decreased during gastrulation [28] and that arrest of the cell cycle is required for both bottle cell formation [20] and for convergent extension movements [21], [22]. We therefore asked whether loss of activin B affects cell division during early embryogenesis.…”

Notch Signaling and Developmental Cell-Cycle Arrest in Drosophila Polar Follicle Cells

“…During development, cell-cycle arrest is critical to controlling cell number, proliferation rate, and organ size. In the early Xenopus gastrula, a G2/M arrest is necessary for bottle-cell formation (Kurth, 2005). During Caenorhabditis elegans development, the CDC-14 phosphatase controls developmental cell-cycle arrest and is required for the quiescent state of specific precursor cells (Saito et al, 2004).…”

The Xenopus Cell Cycle: An Overview

“…In a broader sense, it is still not clear how cell-cycle influences differentiation and vice versa, although roles of specific molecules in regulating cell-cycle events at different cell-cycle stages and in different tissues are emerging, e.g. [150][151][152]. This will clearly be an important area in the future, and Xenopus is a good model system for these studies.…”