Mutation of Semaphorin-6A Disrupts Limbic and Cortical Connectivity and Models Neurodevelopmental Psychopathology
Figure 2
Defects in piriform cortex and olfactory projections.
(A, B) NeuN-immunohistochemistry of coronal P10 brains sections demonstrates a greatly exaggerated folding of the piriform cortex in Sema6A−/− (B), compared to Sema6A+/− mice (A). (C–F) E16 Sema6A+/− (C, D) and Sema6A−/− (E, F) brain sections immunostained for L1 (green) to label all fibres and for Neuropilin-1 (NP-1) to label more specifically LOT axons. In Sema6A−/− mutants, the L1/NP-1 double-stained LOT (yellow) appears rounded and more embedded into layer 1 of the piriform cortex (E) in contrast to a superficially located LOT in Sema6A+/− mice (C). In addition, the LOT extends far further caudally than normal (compare F and D). (G–N) Series of PLAP-stained adult brain sections, showing persistence of a more rounded and displaced LOT (arrowheads) that extends further caudally in Sema6A−/− mutants (K–N) when compared with Sema6A+/− mice (G–J). Note also that adult Sema6A−/− mutants show an exaggerated folding of the pirifom cortex, which extends far caudally. Ia: agranular insular cortex; lot: lateral olfactory tract; Pir: piriform cortex. Scale bar in (A) is for (A, B): 200 µm; in (C) is for (C–D): 100 µm; in (G) is for (G–N): 500 µm.