Phenotype of conditional Sp8 mutants. (a, b) WMISH of Sp8 in E8.5 and E9.5 embryos. Sp8 is strongly expressed in the anterior neural ridge and in the forebrain neuroepithelium at E8.5 (a). At E9.5, Sp8 expression covers the putative forebrain vesicle (b). (c) Foxg1-Cre activity, visualized by X-Gal staining, is evident throughout the telencephalon at E10.5. (d) Cre recombination ablates Sp8 expression in the telencephalon and olfactory placode of cKO at E10.5. (e, f") Histological (nissl stained) coronal sections at E18.5. (e', f') Mutant brains miss the septum and reveal a reduced size of the telencephalon. (e', e") Callosal fibers do not cross the midline and form probst bundles unilaterally. (g, g') On (nissl stained) sagittal sections, a strongly reduced cortical diameter is characteristic for cKO at E18.5. With 15% penetrance, cKO brains show an enhanced phenotype, highlighted by the complete absence of midline derivates. These mutants were termed 'cKO no midline' (e", f"). cKO and 'cKO no midline' only differ at rostral levels of the forebrain. In 'cKO no midline' specimens, a delamination of the cortex from the basal telencephalon is apparent medially, as a visible hole (asterisk in e"). Caudally in the brain, the difference between low and high penetrance of the phenotypes is not significant (f', f"). AC, anterior commissure; ANR, anterior neural ridge; CC, corpus callosum; CP, cortical plate; CTX, cortex; DI, diencephalon; FB, forebrain; HC, hippocampus; IZ, intermediate zone; LGE, lateral ganglionic eminence; MB, midbrain; MZ, marginal zone; OP, olfactory placode; PB, probst bundles; POA, preoptic area; SE, septum; SP, subplate; SVZ, subventricular zone; TH, thalamus; VZ, ventricular zone.