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ATRX is required for maintenance of the neuroprogenitor cell pool in the embryonic mouse brain.

Ritchie K, Watson LA, Davidson B, Jiang Y, Bérubé NG - Biol Open (2014)

Bottom Line: We observed increased cell cycle exit during early-mid neurogenesis, and a depletion of apical progenitors by late neurogenesis in the Atrx- neocortex, explaining the disproportionate layering.Premature differentiation was associated with an increased generation of outer radial glia (oRG) and TBR2-expressing basal progenitors, as well as increased generation of early-born post-mitotic projection neurons.Atrx deletion also reduced the fidelity of mitotic spindle orientation in apical progenitors, where mutant cells were often oriented at non-parallel angles of division relative to the ventricular surface.

View Article: PubMed Central - PubMed

Affiliation: Departments of Paediatrics and Biochemistry, Children's Health Research Institute, University of Western Ontario, Victoria Research Laboratories, 800 Commissioners Road East, London, ON N6C 2V5, Canada.

No MeSH data available.


Related in: MedlinePlus

Increased cell cycle exit in the Atrx- cortex during early neurogenesis results in increased generation of TBR1+ and SATB2+ early-born neurons.(A) Pregnant female mice were subjected to a 24-hour BrdU pulse prior to sacrifice. Ki67 and BrdU immunostaining in E12.5 (pictured) and E14.5 control and Atrx- cortex. Scale bar: 50 µm. Arrowheads indicate BrdU+Ki67− cells that have exited the cell cycle. Cell cycle exit indices were calculated by measuring the ratio of BrdU+Ki67− cells to total BrdU+ cells in E12.5 (B) and E14.5 (C) control and Atrx- cortex (n = 3). (D) TBR1 and SATB2 immunostaining in E14.5 control and Atrx- cortex. Scale bar: 50 µm. (E) Quantification of the proportion of TBR1+ and SATB2+ cells as a percentage of total DAPI+ cells (n = 3). Data expressed as mean ± S.E.M. *P<0.05.
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f03: Increased cell cycle exit in the Atrx- cortex during early neurogenesis results in increased generation of TBR1+ and SATB2+ early-born neurons.(A) Pregnant female mice were subjected to a 24-hour BrdU pulse prior to sacrifice. Ki67 and BrdU immunostaining in E12.5 (pictured) and E14.5 control and Atrx- cortex. Scale bar: 50 µm. Arrowheads indicate BrdU+Ki67− cells that have exited the cell cycle. Cell cycle exit indices were calculated by measuring the ratio of BrdU+Ki67− cells to total BrdU+ cells in E12.5 (B) and E14.5 (C) control and Atrx- cortex (n = 3). (D) TBR1 and SATB2 immunostaining in E14.5 control and Atrx- cortex. Scale bar: 50 µm. (E) Quantification of the proportion of TBR1+ and SATB2+ cells as a percentage of total DAPI+ cells (n = 3). Data expressed as mean ± S.E.M. *P<0.05.

Mentions: Altered postnatal cortical layering could result from precocious differentiation early in neurogenesis, resulting in depletion of the progenitor pool and a failure to generate the correct number of late-born neurons. To determine if the cortical layer abnormalities in the Atrx- cortex were due to increased differentiation of apical progenitor cells, we analyzed the progenitor pool composition, cell cycle exit, and generation of post-mitotic neurons in control and Atrx- cortical cryosections at different developmental time points during the neurogenic period (Figs 2, 3).


ATRX is required for maintenance of the neuroprogenitor cell pool in the embryonic mouse brain.

Ritchie K, Watson LA, Davidson B, Jiang Y, Bérubé NG - Biol Open (2014)

Increased cell cycle exit in the Atrx- cortex during early neurogenesis results in increased generation of TBR1+ and SATB2+ early-born neurons.(A) Pregnant female mice were subjected to a 24-hour BrdU pulse prior to sacrifice. Ki67 and BrdU immunostaining in E12.5 (pictured) and E14.5 control and Atrx- cortex. Scale bar: 50 µm. Arrowheads indicate BrdU+Ki67− cells that have exited the cell cycle. Cell cycle exit indices were calculated by measuring the ratio of BrdU+Ki67− cells to total BrdU+ cells in E12.5 (B) and E14.5 (C) control and Atrx- cortex (n = 3). (D) TBR1 and SATB2 immunostaining in E14.5 control and Atrx- cortex. Scale bar: 50 µm. (E) Quantification of the proportion of TBR1+ and SATB2+ cells as a percentage of total DAPI+ cells (n = 3). Data expressed as mean ± S.E.M. *P<0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4265753&req=5

f03: Increased cell cycle exit in the Atrx- cortex during early neurogenesis results in increased generation of TBR1+ and SATB2+ early-born neurons.(A) Pregnant female mice were subjected to a 24-hour BrdU pulse prior to sacrifice. Ki67 and BrdU immunostaining in E12.5 (pictured) and E14.5 control and Atrx- cortex. Scale bar: 50 µm. Arrowheads indicate BrdU+Ki67− cells that have exited the cell cycle. Cell cycle exit indices were calculated by measuring the ratio of BrdU+Ki67− cells to total BrdU+ cells in E12.5 (B) and E14.5 (C) control and Atrx- cortex (n = 3). (D) TBR1 and SATB2 immunostaining in E14.5 control and Atrx- cortex. Scale bar: 50 µm. (E) Quantification of the proportion of TBR1+ and SATB2+ cells as a percentage of total DAPI+ cells (n = 3). Data expressed as mean ± S.E.M. *P<0.05.
Mentions: Altered postnatal cortical layering could result from precocious differentiation early in neurogenesis, resulting in depletion of the progenitor pool and a failure to generate the correct number of late-born neurons. To determine if the cortical layer abnormalities in the Atrx- cortex were due to increased differentiation of apical progenitor cells, we analyzed the progenitor pool composition, cell cycle exit, and generation of post-mitotic neurons in control and Atrx- cortical cryosections at different developmental time points during the neurogenic period (Figs 2, 3).

Bottom Line: We observed increased cell cycle exit during early-mid neurogenesis, and a depletion of apical progenitors by late neurogenesis in the Atrx- neocortex, explaining the disproportionate layering.Premature differentiation was associated with an increased generation of outer radial glia (oRG) and TBR2-expressing basal progenitors, as well as increased generation of early-born post-mitotic projection neurons.Atrx deletion also reduced the fidelity of mitotic spindle orientation in apical progenitors, where mutant cells were often oriented at non-parallel angles of division relative to the ventricular surface.

View Article: PubMed Central - PubMed

Affiliation: Departments of Paediatrics and Biochemistry, Children's Health Research Institute, University of Western Ontario, Victoria Research Laboratories, 800 Commissioners Road East, London, ON N6C 2V5, Canada.

No MeSH data available.


Related in: MedlinePlus