Figure 1

Microcephaly in perlecan-null embryos. (A-F) Series of Nissl stained coronal sections of E13.5 forebrain at rostral (A, D), middle (B, E) and caudal (C, F) levels. The brains of a wild-type (A-C) and a perlecan-null (D-F) embryos are shown. Note a reduction in the size of the ventral forebrain in the perlecan-null brains, particularly affecting the medial structures, such as MGE, hippocampus, and rostral part of the thalamus. (G) Quantification of pallial, MGE and LGE cross-sectional area per hemisphere in sections at the middle level. Results reveal that whole brain size is reduced variably in perlecan-null embryos, but that at E13.5 all perlecan-null embryos have severely underdeveloped MGE as compared with their wild-type littermates. Two litters at E12.5 and three litters at E13.5 were used; n = 2 embryos at E12.5 and n = 6 embryos at E13.5. ** p < 0.01. (H, I) Nissl stained coronal sections at E15.5 in wild-type (H) and perlecan-null (I) embryos. Ventral forebrain underdevelopment extends significantly to LGE and paleocortex. Note the reduction of cortical plate thickness in the perlecan-null cortex. (J-M) E17.5 wild-type (J, L) and perlecan-null (K, M) embryos. Panels L and M represent enlargements of the regions boxed in J and K, respectively. The ventral forebrain is reduced in size in the perlecan-null embryo, and the cortical plate is thinner. Additionally, in the perlecan-null telencephalon, the onset of neuronal ectopias (arrows in K) is frequent in the most antero-dorsal region of the cerebral hemispheres. (N-P) Antibodies to laminin highlight the meningeal basal lamina, the meninges and the blood vessels in the wild-type (N) and perlecan-null (O and P) embryos. In the perlecan-null, disruption of the basal lamina is observed in an ectopic area (indicated by arrows in O). However, in the rest of the basal surface of the perlecan-null brain, laminin deposition is continuous (P). Scale bars: 250 μm (A-F, H-I), 500 μm (J, K), 50 μm (L, M), 40 μm (N-P). Abbreviations: CGE, caudal ganglionic eminence; CP, cortical plate; Hp, hippocampus; IZ, intermediate zone LGE, lateral ganglionic eminence; MGE, medial ganglionic eminence; P, pallium; Th, thalamus.