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. Author manuscript; available in PMC: 2013 Dec 1.
Published in final edited form as: J Neuropathol Exp Neurol. 2012 Dec;71(12):1047–1063. doi: 10.1097/NEN.0b013e318274a128

Figure 5.

Figure 5

Marked dyslamination and expansion of heterotopia (HT) during late neurogenesis are associated with overmigration of deep and superficial cortical plate (CP) neurons. (A-H) The Tbr1-positive CP layer VI in Dag1+/+ brains progressively expands between E14.5 (A), E15.5 (C), and E18.5 (E). In addition to CP layer VI, small numbers of heterotopic Tbr1-positive neurons are present in Dag1 conditional knockout (cKO) (Dag1−/−) E14.5 brains (B, arrows). Many more heterotopic Tbr1-positive neurons are present at E15.5 (D) compared to E14.5 (B) and the thickness of Tbr1-positive cells in layer VI (D) appears much reduced at E15.5 in Dag1 cKO brains compared to wild type (WT) Dag1+/+ brains (C). Despite substantial expansion of meningeal HT, few additional heterotopic Tbr1-positive neurons are present in Dag1 cKO E18.5 brains (F) compared to E15.5 brains (D), and many areas in layer VI still have large numbers of appropriately-laminated Tbr1-positive cells at E18.5 (F, arrow). (I-N) Many early-born Tbr1-positive/BrdU-positive (E12.5) neurons (arrow) are present in Dag1 cKO P0.5 HT despite birth dates several days prior to BM disruption (G, HT). Although occasional late-born Tbr1-positive/BrdU-positive (E15.5) neurons (arrow) are present in Dag1 cKO P0.5 HT, many late-born Tbr1-positive neurons are appropriately laminated in CP layer VI despite BM disruption prior to their birth and migration (H, layer VI). (I-N) Many late-born Cux1-positive neurons are present in layers II-IV in Dag1+/+ brains at E15.5 (I), E16.5 (K) and P0.5 (M). Small numbers of heterotopic Cux1-positive neurons are present in Dag1 cKO E15.5 brains (J, arrows) whereas slightly more and substantially more are present at E16.5 (L) and P0.5 (N), respectively. Despite widespread BM disruption prior to their birth and migration through the CP, many Cux1-positive neurons are appropriately laminated in layers II-IV at P0.5 (N). (O, P) Er81-positive neurons are restricted to the deep aspect of layer V in P0.5 Dag1+/+ brains (O) but are present in layers I-V and heterotopia (arrow) in Dag1 cKO brains (P). (Q, R) Rorβ-positive neurons are only present in layer IV in P0.5 Dag1+/+ brains (Q) but are distributed throughout layers I-IV (arrow) in Dag1 cKO brains (R). (S, T) CTIP2-positive neurons are mostly limited to layer V and are superficial to earlier-born Tbr1-positive neurons in layer VI in P0.5 Dag1+/+ brains (S) but Tbr1-positive neurons are also admixed with CTIP2-positive neurons in layers I-V and heterotopia in Dag1 cKO brains (T). (U, V) Cux1-positive neurons in layers II-IV are superficial to earlier-born CTIP2-positive neurons in layer V in Dag1+/+ brains (U) but are also admixed with Cux1-positive cells in layers I-IV and HT in Dag1 cKO brains (V). IZ, intermediate zone; SVZ, subventricular zone. Scale bars: A-F, 200 µm; I-N, 100 µm; G, H, O–V, 50 µm.