Fig. 1. Neuroanatomy of megalin-deficient neonates and embryos. (A,B) External appearance of wild-type (A) and megalin^–/– neonates (B), highlighting craniofacial abnormalities in the receptor-deficient mouse. (C,D) Coronal H+E stained sections through the rostral brain of E18.5 embryos, depicting enlarged ventricles in the megalin-deficient animal (D) compared with the control (C). (E,F) Horizontal sections through the brain at E18.5, demonstrating a single cerebral hemisphere with a central fused ventricle in the megalin^–/– embryo (F) compared with bilateral hemispheres with two lateral ventricles in the control (E). (G-I) Coronal forebrain sections of wild-type (G) and megalin^–/– E14.5 embryos (H,I), with abnormalities ranging from enlarged ventricles (H) to exencephalus and a common ventricular system (I). (K-N) Sagittal forebrain sections from wild type (K,L) and megalin-deficient E12.5 embryos (M,N) subjected to H+E staining (K,M) or detection of cell death by TUNEL assay (L,N). megalin^–/– embryos suffer from a reduction in neuroepithelial wall thickness (M, arrowhead) compared with controls (K) that coincides with massive apoptosis in the roof of the cerebral cortex (N, arrowhead). (O,P) Lateral aspects of wild-type (O) and megalin^–/– (P) E10.5 embryos. Note the reduced size of the telencephalic vesicles in the knockout. (Q,R) Coronal forebrain sections, indicating a decrease in thickness of the ventral neuroepithelium that is most pronounced in the AEP and the MGE of megalin^–/– embryos (R) compared with megalin^+/+ embryos (Q). (C-M,O-R: H+E staining). AEP, anterior entopeduncular area; MGE, medial ganglionic eminence; tv, telencephalic vesicles.