Nkx2-2, a homeodomain transcription factor, is crucial in governing cell fate decisions in multiple organs such as the central nervous system (CNS), pancreas, intestine, and taste system [2,3]. In the CNS, it is an effector molecule of the Sonic Hedgehog pathway, essential for V3 domain specification during neural tube patterning and oligodendrocyte maturation [1]. In the pancreas, it is critical for α -cell identity, directly activating α -cell genes and repressing alternate islet cell fate genes [4]. Genetic models, like KO/CKO mouse models, are valuable for studying its functions.

In Nkx2-2 knockout mice, severe neonatal diabetes occurs, along with changes in β -cell progenitor fate into ghrelin-producing cells, mimicking the human condition of recessive NKX2-2 gene mutations causing neonatal diabetes, obesity, and developmental delay [6]. In taste cells, neonatal Nkx2-2-knockout mice do not express key type III taste cell marker genes, indicating Nkx2-2 is critical for the development of type III taste cells in the posterior tongue [3]. Also, overexpression of NKX2-2 in osteosarcoma cells in vitro and in vivo suppresses tumor growth and metastasis, acting as a tumor suppressor by downregulating genes like COL5A2, PLAU, SEMA7A, and S1PR1 [5].

In conclusion, Nkx2-2 plays essential roles in organ development and cell-fate determination, especially in the CNS, pancreas, taste system, and has implications in diseases like neonatal diabetes and osteosarcoma. Studies using KO/CKO mouse models have been instrumental in uncovering these functions, providing insights into disease mechanisms and potential therapeutic targets.