Dlx5, or distal-less homeobox 5, is a crucial transcription factor. It is essential for initiating osteoblast differentiation by driving Runt-related transcription factor 2 expression, and thus plays a significant role in bone development [1,3]. It is also involved in the differentiation of PV-interneurons during brain development and has a continued low-level expression in adult telencephalic GABAergic neurons [2].

In mouse models, targeted deletion of Dlx5/6 in GABAergic neurons (Dlx5/6VgatCre mice) leads to altered behavioral and metabolic profiles, with a linear correlation between Dlx5/6 allelic dosage and the density of PV-positive neurons in the adult prelimbic cortex and hippocampus, as well as with anxiety and compulsivity-like behaviors [2]. In osteosarcoma, knockdown of Dlx5 in cell lines inhibits cell growth and progression, and induces apoptosis and cell cycle changes both in vitro and in vivo, suggesting an oncogenic role for Dlx5 in this primary bone cancer, potentially through activation of the NOTCH signaling pathway [3].

In conclusion, Dlx5 has diverse functions in different biological processes. Its role in bone development and cancer, especially osteosarcoma, is well-demonstrated through mouse models. Understanding Dlx5's functions provides insights into bone-related diseases and certain neuropsychiatric conditions, offering potential targets for therapeutic interventions.