All Phenotypes Rbm8a<tm1Dlsi> MGI Mouse

microcephaly ( J:221648 )

• severe microcephaly at P0 and P12

• microcephaly arises during embryogenesis between E11.5 and E12.5, with marked microcephaly noted by E14.5

abnormal radial glial cell apoptosis ( J:221648 )

• at E12.5, ~7% of all Pax6+ radial glia undergo apoptosis

• at E12.5, radial glia apoptosis is less extensive than neuronal apoptosis, with ~7% of all Pax6+ radial glia undergoing apoptosis versus 21% of all Tuj1+ neurons

increased forebrain apoptosis ( J:221648 )

• at E11.5, a slight increase in apoptosis is observed in dorsal neocortices relative to controls, as shown by cleaved-caspase3 (CC3) and TUNEL staining

• by E12.5, extensive apoptosis is detected throughout the thickness of the neocortex and is especially high in basal layers (cortical plate and subplate), where neurons reside following migration

abnormal radial glial cell morphology ( J:221648 )

• at E13.5, the remaining radial glia in the neocortex appear disorganized

decreased radial glial cell number ( J:221648 )

• although the number of Pax6+ radial glial cells is normal at E11.5, a 54% reduction in radial glia density in seen in the developing neocortex by E12.5

• in culture, primary dissociated cells from E12.5 dorsal neocortices show a 1.5-fold reduction in Pax6+ radial glia relative to controls; a 2-fold decrease in radial glia is noted at E13.5

impaired neuron differentiation ( J:221648 )

• neurogenesis defects affecting progenitor proliferation, progenitor and neuron number, and apoptosis

premature neuronal precursor differentiation ( J:221648 )

• in culture, primary dissociated cells from E11.5 dorsal neocortices show a significantly lower fraction of EdU+Ki67+ cycling progenitors relative to controls, indicating that a higher fraction of progenitors have exited the cell cycle

• increased cell-cycle exit is associated with a significantly higher fraction of EdU+Tuj1+, consistent with an increased neuron number

increased neuronal precursor proliferation ( J:221648 )

• significant increase in cortical progenitor proliferation at E11.5 relative to controls, as determined by phospho-histone3 (PH3) staining

abnormal telencephalon development ( J:221648 )

• by E14.5, the ventricle and dorsal telencephalon are severely reduced

decreased brain size ( J:221648 )

• brains are ~70% smaller at P12

small brain ventricles ( J:221648 )

• by E14.5

abnormal cerebral cortex morphology ( J:221648 )

• significant reduction in the dorsal surface area of the cortex at P12

decreased neocortex size ( J:221648 )

• markedly thinner neocortex by E13.5

• most of the neocortex is missing at P0

abnormal stratification in cerebral cortex ( J:221648 )

• severe cortical lamination defects including loss of virtually all upper layer neurons

• at P0, remaining neocortical tissue shows a significant reduction of both Cux1+ (layers II/III) and Foxp1+ (layers III-V) neurons relative to controls

• although the density of Tbr1+ (layer VI) neurons is not significantly reduced at P0, Tbr1+ neurons are improperly distributed throughout the cortical tissue

thin cerebral cortex ( J:221648 )

• although brains show normal cortical thickness in dorsal neocortices at E11.5, cortices are 21% thinner by E12.5

• by E13.5, dorsal cortices are 50% thinner than in control brains; seen in both dorsal and more lateral cortical regions

decreased neuronal precursor cell number ( J:221648 )

• at E13.5, the density of Tbr2+ intermediate progenitors in the developing neocortex is reduced by 87%

increased neuron number ( J:221648 )

• significant increase in Tbr1+ deep-layer neurons in the neocortex at E12.5 relative to controls

• in culture, primary dissociated cells from E12.5 dorsal neocortices show a 2.7-fold increase in Tuj1+ immature neurons relative to controls; a similar (2.5-fold) increase in neuron number is noted at E13.5

ectopic cortical neuron ( J:221648 )

• although the relative distribution of Tuj1+ immature neurons is normal at E11.5, the layer of Tuj1+ neurons in the developing neocortex is strikingly expanded by E12.5

• at E13.5, Tuj1+ neurons are detected throughout the thickness of the dorsal neocortex, indicating aberrant distribution of postmitotic neurons