Cerebral Cortex Advance Access published online on December 7, 2007
Cerebral Cortex, doi:10.1093/cercor/bhm209
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Foxg1 Haploinsufficiency Reduces the Population of Cortical Intermediate Progenitor Cells: Effect of Increased p21 Expression
1 Department of Neuroscience and Physiology, State University of New York–Upstate Medical University, 750 East Adams Street, Syracuse, NY 13210, USA, 2 Developmental Exposure Alcohol Research Center, Binghamton University, Binghamton, NY 13902, USA, 3 State University of New York-Cortland, Cortland, NY 13045, 4 Research Service, Veterans Affairs Medical Center, Syracuse, NY 13210, USA
Address correspondence to email: millermw{at}upstate.edu.
Foxg1 is a transcription factor that is critical for forebrain development. Foxg1+/Cre mice were used to test the hypotheses 1) that the subventricular zone (SZ) generates supragranular neurons, 2) that Foxg1-regulated activities define the output from the SZ, and 3) that Foxg1 is involved in the suppression of p21-initiated cell-cycle exit. Foxg1+/Cre mice have thinner neocortices than wild-type controls, specifically in the supragranular layers, as detected by Brn2 immunostaining. Cell proliferation in the ventricular zone (VZ) and SZ was examined to investigate the reduction in upper layer neurons. The number of cycling VZ cells was similar in Foxg1+/+ and Foxg1+/Cre brains. Interestingly, cell proliferation in the SZ and intermediate progenitor cell (IPC) production (noted by Tbr2-immunostaining) was reduced in Foxg1+/Cre brains. These decreases coincided with increased expression of the cell-cycle inhibitor p21 in the VZ and SZ. Furthermore, colocalization of p21 with markers of cell proliferation and IPCs indicated that p21 was temporally expressed to influence the proliferative fate of IPCs. Thus, the present data are consistent with the above hypotheses, particularly, that during corticogenesis, Foxg1-regulated activities enable the expansion of the IPC population likely through suppression of p21-dependent cell-cycle exit.
Key Words: cell cycle • Ki-67 • p27 • progenitor cells • subventricular zone • ventricular zone
Julie A. Siegenthaler and Barbara A. Tremper-Wells have contributed equally to this work.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  S. J. Arnold, G.-J. Huang, A. F.P. Cheung, T. Era, S.-I. Nishikawa, E. K. Bikoff, Z. Molnar, E. J. Robertson, and M. Groszer The T-box transcription factor Eomes/Tbr2 regulates neurogenesis in the cortical subventricular zone Genes & Dev., September 15, 2008; 22(18): 2479 - 2484. [Abstract] [Full Text] [PDF]
|
|