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The mamillary body (MM) is a group of hypothalamic nuclei related to memory and spatial navigation that interconnects hippocampal, thalamic, and tegmental regions. Here we demonstrate that  Lhx5 , a LIM-HD domain transcription factor expressed early in the developing posterior hypothalamus, is required for the generation of the MM and its derived tracts. The MM markers  Foxb1 ,  Sim2 , and  Lhx1  are absent in Lhx5 knock-out mice from early embryonic stages, suggesting abnormal specification of this region. This was supported by the absence of  Nkx2.1  and expansion of  Shh  in the prospective mamillary area. Interestingly, we also found an ectopic domain expressing  Lhx2  and  Lhx9  along the anterio-posterior hypothalamic axis. Our results suggest that Lhx5 controls early aspects of hypothalamic development by regulating gene expression and cellular specification in the prospective MM.

LIM homeobox protein 5 (Lhx5) is essential for mamillary body development