Winged helix transcription factor Foxb1 is essential for access of mammillothalamic axons to the thalamus

Our aim was to study the mechanisms of brain histogenesis, As a model, we h ave used the role of winged helix transcription factor gene Foxb1 in the em ergence of a very specific morphological trait of the diencephalon, the mam millary axonal complex, Foxb1 is expressed in a large hypothalamic neuronal group (the mammillary body), which gives origin to a major axonal bundle w ith branches to thalamus? tectum and tegmentum, We have generated mice carr ying a targeted mutation of Foxb1 plus the tau-lacZ reporter. In these muta nts, a subpopulation of dorsal thalamic ventricular cells ("thalamic palisa de") show abnormal persistence of Foxb1 transcriptional activity; the thala mic branch of the mammillary axonal complex is not able to grow past these cells and enter the thalamus, The other two branches of the mammillary axon al complex (to tectum and tegmentum) are unaffected by the mutation. Most o f the neurons that originate the mammillothalamic axons suffer apoptosis af ter navigational failure. Analysis of chimeric brains with wild-type and Fo xb1 mutant cells suggests that correct expression of Foxb1 in the thalamic palisade is sufficient to rescue the normal phenotype. Our results indicate that Foxb1 is essential for diencephalic histogenesis and that it exerts i ts effects by controlling access to the target by one particular axonal bra nch.