Restricted expression of cdc25a in the tailbud is essential for formation of the zebrafish posterior body

Abstract

The vertebrate body forms from a multipotent stem cell-like progenitor population that progressively contributes newly differentiated cells to the most posterior end of the embryo. How the progenitor population balances proliferation and other cellular functions is unknown due to the difficulty of analyzing cell division in vivo. Here, we show that proliferation is compartmentalized at the posterior end of the embryo during early zebrafish development by the regulated expression of cdc25a, a key controller of mitotic entry. Through the use of a transgenic line that misexpresses cdc25a, we show that this compartmentalization is critical for the formation of the posterior body. Upon misexpression of cdc25a, several essential T-box transcription factors are abnormally expressed, including Spadetail/Tbx16, which specifically prevents the normal onset of myoD transcription, leading to aberrant muscle formation. Our results demonstrate that compartmentalization of proliferation during early embryogenesis is critical for both extension of the vertebrate body and differentiation of the multipotent posterior progenitor cells to the muscle cell fate.

Cdc25 and the importance of G2control

“…3A). 33 Zebrafish embryos continue to express cdc25 within the cells that undergo gastrulation, 41 demonstrating that unrestricted Cdc25 does not affect gastrulation in all model systems, and instead depends on the type of cell movements that underlie the EMT.…”

“…Recent work has established a clear connection between proliferation and the expression of cdc25a during posterior growth in zebrafish; intriguingly, the posterior progenitors were found to be cdc25a negative and quiescent. 41 As cells move through differentiation, 2 cycles of cdc25a expression are initiated, which, in turn, activates 2 rounds of cell division (Fig. 4B).…”

“…4B). 41,46 If Cdc25a is ubiquitously expressed in zebrafish embryos during posterior growth, development is severely perturbed. 41 Why is the cell cycle so tightly regulated during this process?…”

“…41,46 If Cdc25a is ubiquitously expressed in zebrafish embryos during posterior growth, development is severely perturbed. 41 Why is the cell cycle so tightly regulated during this process? Surprisingly, forced expression of Cdc25a prevented the normal differentiation of muscle cells, because the cells remained trapped in an early precursor state due to the aberrant maintenance of a key early differentiation gene that is normally only transiently expressed.…”

“…Surprisingly, forced expression of Cdc25a prevented the normal differentiation of muscle cells, because the cells remained trapped in an early precursor state due to the aberrant maintenance of a key early differentiation gene that is normally only transiently expressed. 41,47 Thus, regulated Cdc25 expression is essential for normal differentiation during posterior body growth and is involved in maintaining proper gene expression.…”