FoxM1-driven cell division is required for neuronal differentiation in early Xenopus embryos.
In vertebrate embryogenesis, neural induction is the earliest step through which the fate of embryonic ectoderm to neuroectoderm becomes determined. Cells in the neuroectoderm or neural precursors actively proliferate before they exit from the cell cycle and differentiate into neural cells. However, little is known about the relationship between cell division and neural differentiation, although, in Xenopus, cell division after the onset of gastrulation has been suggested to be nonessential for neural differentiation. Here, we show that the Forkhead transcription factor FoxM1 is required for both proliferation and differentiation of neuronal precursors in early Xenopus embryos. FoxM1 is expressed in the neuroectoderm and is required for cell proliferation in this region. Specifically, inhibition of BMP signaling, an important step for neural induction, induces the expression of FoxM1 and its target G2-M cell-cycle regulators, such as Cdc25B and cyclin B3, thereby promoting cell division in the neuroectoderm. Furthermore, G2-M cell-cycle progression or cell division mediated by FoxM1 or its target G2-M regulators is essential for neuronal differentiation but not for specification of the neuroectoderm. These results suggest that FoxM1 functions to link cell division and neuronal differentiation in early Xenopus embryos.
Ueno
Hiroyuki
H
Department of Biology, Graduate School of Sciences, Kyushu University, Hakozaki 6-10-1, Fukuoka 812-8581, Japan.
Nakajo
Nobushige
N
Watanabe
Minoru
M
Isoda
Michitaka
M
Sagata
Noriyuki
N
D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000037:antagonists & inhibitors; D002352:Carrier Proteins / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D002455:Cell Division / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors / Q000235:genetics* / Q000502:physiology; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D015151:Immunoblotting; D017403:In Situ Hybridization; D008954:Models, Biological; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D029867:Xenopus Proteins / Q000235:genetics* / Q000502:physiology; D014982:Xenopus laevis / Q000196:embryology / Q000235:genetics*; D000099176:Noggin Protein
D019485:Bone Morphogenetic Proteins; D002352:Carrier Proteins; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors; D029867:Xenopus Proteins; D000099176:Noggin Protein; C504436:FoxM1 protein, Xenopus