Abstract: BACKGROUND: Recent studies have revealed that Distal-less(Dlx) homeobox genes play an important role in the induction of osteogenic differentiation of odontogenic cells and can participate in the regulation of various osteogenic-related signaling pathways or affect the expression of key osteogenic transcription factors. The regulatory effects of Dlx genes may provide new ideas and methods for clinical periodontal tissue regeneration studies.  
OBJECTIVE: To review research progress on the role and mechanisms of the Dlx gene family in the osteogenic differentiation of odontogenic cells.
METHODS: Literature retrieval was conducted in PubMed, CNKI, and WanFang databases. The search terms were “distal-less homeobox gene, distal-less homeobox,  Dlx, Dlx gene, bone-formation, osteogenesis, bone formation, ossification, ossifications, osteoclastogenesis, osteoclastogeneses, endochondral ossification, dental,oral, odontogenic, dental stem cell” in English and Chinese, respectively. Studies of low quality and irrelevant to the topic of the article were excluded. Finally, the included 82 articles were read, analyzed and summarized.  
RESULTS AND CONCLUSION: (1) Homeobox genes are important genes that determine the growth and development of the body. Homeobox genes are composed of many families. Among them, the important osteogenic gene family is the Dlx gene family. The development of tooth germ is mainly related to two homeobox genes: MSX gene family and Dlx gene family. The latter plays an important role in the development of tooth germ and the differentiation of odontogenic cells. (2) The positive and negative feedback regulation of Dlx3 gene on BMP and Notch signaling pathway, and the osteogenic induction mechanism of Dlx3 gene overexpression on transcription factors zbtb16 and EGR1 are clarified. (3) Dlx2/3/5 can affect osteogenesis in dental follicle cells, which may be due to similar homologous domain external structure and chromosome localization. (4) Exploring the effects of of Dlx genes on dental tissues revealed that these complex molecular signaling and cell-cell ordering interactions involve the disturbance of the behavior of neural crest mesenchymal or its connective tissue matrix, resulting in many abnormalities of oral tooth morphology and maxillofacial bone. Therefore, all kinds of odontogenic transcription factors need to be strictly regulated in time and space and in their quantitative output. (5) Studies have confirmed the mechanism of Dlx gene family in the osteogenic differentiation of osteoblasts, chondroblasts and mesenchymal stem cells. With the continuous development of technology and in-depth research, the regulation and molecular signal mechanism of Dlx gene family on osteogenic differentiation of odontogenic cells will be further clarified.

Key words: distal-less homeobox gene, Dlx gene, Dlx, bone formation, dental, odontogenic, dental stem cell