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

[alpha-thalassemia]

Mutations in the alpha-thalassemia mental retardation X-linked (ATRX ) gene cause a spectrum of abnormalities including intellectual disability , developmental delay , seizures , and microcephaly . The ATRX protein is highly enriched at heterochromatic repetitive sequences adjacent to the centromere , and ATRX depletion results in chromosome congression , segregation , and cohesion defects . Here , we show that Cre-mediated inactivation of Atrx in the embryonic mouse (Mus musculus ) brain results in expansion of cerebral cortical layer VI , and a concurrent thinning of layers II -IV . We observed increased cell cycle exit during early -mid neurogenesis , and a depletion of apical progenitors by late neurogenesis in the Atrx-null neocortex , explaining the disproportionate layering . Premature differentiation was associated with an increased generation of outer radial glia (oRG ) and TBR 2 -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 . We conclude that ATRX is required for correct lamination of the mouse neocortex by regulating the timing of neuroprogenitor cell differentiation .

Diseases
Validation

Diseases presenting "heterochromatic repetitive sequences" symptom

alpha-thalassemia

You can validate or delete this automatically detected symptom