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Studies on crown dentin formation have been a major focus in tooth development for several decades. Interestingly, the population prevalence for genetic short root anomaly (SRA) with no apparent defects in crown is close to 1.3%. Furthermore, people with SRA itself are predisposed to root resorption during orthodontic treatment. The discovery of the unique role of Nfic (nuclear factor I C; a transcriptional factor) in controlling root but not crown dentin formation points to a new concept: tooth crown and root have different control mechanisms. Further genetic mechanism studies have identified more key molecules (including Osterix, \u03b2-catenin, and sonic hedgehog) that play a critical role in root formation. Extensive studies have also revealed the critical role of Hertwig\u2019s epithelial root sheath in tooth root formation. In addition, Wnt10a has recently been found to be linked to multirooted tooth furcation formation. These exciting findings not only fill the critical gaps in our understanding about tooth root formation but will aid future research regarding the identifying factors controlling tooth root size and the generation of a whole \u201cbio-tooth\u201d for therapeutic purposes. This review starts with human SRA and mainly focuses on recent progress on the roles of NFIC-dependent and NFIC-independent signaling pathways in tooth root formation. Finally, this review includes a list of the various Cre transgenic mouse lines used to achieve tooth root formation\u2013related gene deletion or overexpression, as well as strengths and limitations of each line.<\/jats:p>","DOI":"10.1177\/0022034517717478","type":"journal-article","created":{"date-parts":[[2017,7,7]],"date-time":"2017-07-07T10:28:34Z","timestamp":1499423314000},"page":"1221-1228","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":79,"title":["Signaling Pathways Critical for Tooth Root Formation"],"prefix":"10.1177","volume":"96","author":[{"given":"J.","family":"Wang","sequence":"first","affiliation":[{"name":"Biomedical Sciences, Texas A&M College of Dentistry, Dallas, TX, USA"},{"name":"State Key Laboratory of Oral Diseases, Department of Periodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, 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