Ongoing expression of Nkx2.1 in the postnatal mouse forebrain: potential for understanding NKX2.1 haploinsufficiency...

Coordinated movements require the caudate-putamen and the globus pallidus, two nuclei belonging to the basal ganglia, to be intact and functioning properly. Many neurons populating these regions derive from the medial ganglionic eminence, a transient structure that expresses the transcription factor Nkx2.1 during prenatal development. Accordingly, the basal ganglia of Nkx2.1(-/-) mice are heavily affected and a substantial loss of several types of GABAergic interneurons has been observed. Interestingly, heterozygous mutation of the NKX2.1 gene in humans has been described as causing an unusual disorder from the second year of life onwards, which is mainly characterized by disturbances of motor abilities and delayed speech development. In the present study, we therefore investigated whether Nkx2.1 is still expressed in the young adult and aged mouse forebrain. After birth, the most intense immunolabeling for Nkx2.1 was detected in several components of the hypothalamic region, in the subventricular zone of the ventral tips lining the lateral ventricles, and in neighboring structures including the striatum, the globus pallidus and the various nuclei of the septal complex. Surprisingly, this staining pattern was substantially maintained into adulthood. Double immunocytochemistry for Nkx2.1 and various neuronal markers revealed that mainly parvalbumin-containing GABAergic neurons, but also cholinergic neurons, of the ventral forebrain express this protein. Moreover, in situ hybridization confirmed that these neurons maintain synthesis of Nkx2.1 throughout life. The robust expression of Nkx2.1 by these neurons points to a broad functional spectrum within the adult forebrain.