Formation and patterning of the forebrain and olfactory system by zinc-finger genes Fezf1 and Fezf2

The zinc finger genes Fezf1 (Fez) and Fezf2 (Fez-like, Fezl, Zfp312) were initially identified as anterior neuroectoderm-specific genes in Xenopus and zebrafish. They encode transcriptional regulators containing an Engrailed homology 1 (Eh1) repressor motif, which is known to interact with Groucho/TLE (Transducin-Like Enhancer of Split)-type transcriptional co-repressors. Both Fezf1 and Fezf2 are expressed in the prospective forebrain region during early embryogenesis, and they subsequently show both overlapping and distinct expression domains in the olfactory epithelium and forebrain. Loss-of-function studies in mouse and zebrafish revealed roles for Fezf1 and Fezf2 in the development of the olfactory system and forebrain. In mice, Fezf1, expressed in olfactory sensory neurons, is required for the axonal projection of olfactory sensory neurons, and controls the layer formation of the olfactory bulb in a non-cell autonomous manner. Fezf2 is involved in the differentiation of subplate neurons and the formation of the fimbria and fornix. Fezf2 is also essential for specification of the subcerebral projection neurons in the neocortex. Fezf1 and Fezf2 control the rostro-caudal patterning of the diencephalon by repressing the caudal diencephalon fate in the rostral diencephalon in mice and zebrafish. In zebrafish, fezf2 is also required for the development of monoaminergic (dopaminergic and serotonergic) neurons in the basal forebrain.