Cell-cycle-specific nestin expression coordinates with morphological changes in embryonic cortical neural progenitors.
During brain development, neural progenitor cells extend across the thickening brain wall and undergo mitosis. To understand how these two completely different cellular events are coordinated, we focused on the transcription pattern of the nestin gene (Nes), which encodes an intermediate filament protein strongly expressed in neural progenitor cells. To visualize nestin expression in vivo, we generated transgenic mice that expressed a destabilized fluorescent protein under the control of Nes second intronic enhancer (E/nestin:dVenus). During the neurogenic stage, when the brain wall thickens markedly, we found that nestin was regulated in a cell-cycle-dependent manner. Time-lapse imaging showed that nestin gene expression was upregulated during G1-S phase, when the neural progenitor cells elongate their fibers. However, nestin expression dramatically declined in G2-M phase, when progenitor cells round up to undergo mitosis. The cell-cycle-dependent phosphorylation of an upstream regulator class III POU transcription factor (Pou3f2 or Brn2) reduced its binding activity to the nestin core enhancer element and was therefore responsible for the decreased Nes transcription in G2-M phase. Collectively, these findings demonstrate precisely orchestrated gene regulation that correlates with the 3D morphological changes in neural progenitor cells in vivo.
Sunabori
Takehiko
T
Department of Physiology, Keio University School of Medicine, Tokyo 160-8582, Japan.
Tokunaga
Akinori
A
Nagai
Takeharu
T
Sawamoto
Kazunobu
K
Okabe
Masaru
M
Miyawaki
Atsushi
A
Matsuzaki
Yumi
Y
Miyata
Takaki
T
Okano
Hideyuki
H
D000818:Animals; D002453:Cell Cycle; D024202:Electrophoretic Mobility Shift Assay; D053595:Embryonic Stem Cells / Q000166:cytology*; D005260:Female; D007381:Intermediate Filament Proteins / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009420:Nervous System / Q000166:cytology*; D064231:Nestin; D011247:Pregnancy
D007381:Intermediate Filament Proteins; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; D064231:Nestin