Msx1 is essential for proper rostral tip formation of the mouse mandible

Saori Shibuya; Mitsushiro Nakatomi; Kaori Kometani-Gunjigake; Kayoko Nakao-Kuroishi; Kae Matsuyama; Shinji Kataoka; Takashi Toyono; Yuji Seta; Tatsuo Kawamoto

doi:10.1016/j.bbrc.2022.12.047

Msx1 is essential for proper rostral tip formation of the mouse mandible

Biochem Biophys Res Commun. 2023 Jan 29:642:75-82. doi: 10.1016/j.bbrc.2022.12.047. Epub 2022 Dec 18.

Authors

Saori Shibuya¹, Mitsushiro Nakatomi², Kaori Kometani-Gunjigake³, Kayoko Nakao-Kuroishi³, Kae Matsuyama⁴, Shinji Kataoka⁴, Takashi Toyono⁴, Yuji Seta⁴, Tatsuo Kawamoto³

Affiliations

¹ Division of Orofacial Functions and Orthodontics, Department of Health Promotion, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu, 803-8580, Japan; Division of Anatomy, Department of Health Promotion, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu, 803-8580, Japan.
² Department of Human, Information and Life Sciences, School of Health Sciences, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, 807-8555, Japan. Electronic address: nktm@health.uoeh-u.ac.jp.
³ Division of Orofacial Functions and Orthodontics, Department of Health Promotion, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu, 803-8580, Japan.
⁴ Division of Anatomy, Department of Health Promotion, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu, 803-8580, Japan.

PMID: 36566565
DOI: 10.1016/j.bbrc.2022.12.047

Abstract

The right and left mandibular processes derived from the first branchial arch grow toward the midline and fuse to create the rostral tip region of the mandible during mandibular development. Severe and mild cases of failure in this process results in rare median cleft of the lower lip and cleft chin, respectively. The detailed molecular mechanisms of mandibular tip formation are unknown. We hypothesize that the Msx1 gene is involved in mandibular tip development, because Msx1 has a central role in other craniofacial morphogenesis processes, such as teeth and the secondary palate development. Normal Msx1 expression was observed in the rostral end of the developing mandible; however, a reduced expression of Msx1 was observed in the soft tissue of the mandibular tip than in the lower incisor bud region. The rostral tip of the right and left mandibular processes was unfused in both control and Msx1-null (Msx1^-/-) mice at embryonic day (E) 12.5; however, a complete fusion of these processes was observed at E13.5 in the control. The fused processes exhibited a conical shape in the control, whereas the same region remained bifurcated in Msx1^-/-. This phenotype occurred with 100% penetrance and was not restored at subsequent stages of development. Furthermore, Meckel's cartilage in addition to the outline surface soft tissues was also unfused and bifurcated in Msx1^-/- from E14.5 onward. The expression of phosho-Smad1/5, which is a mediator of bone morphogenetic protein (Bmp) signaling, was downregulated in the mandibular tip of Msx1^-/- at E12.5 and E13.5, probably due to the downregulated Bmp4 expression in the neighboring lower incisor bud. Cell proliferation was significantly reduced in the midline region of the mandibular tip in Msx1^-/- at the same developmental stages in which downregulation of pSmad was observed. Our results indicate that Msx1 is indispensable for proper mandibular tip development.

Keywords: Growth and development; Homeodomain proteins; Lower jaw; Mandibular bone; Meckel's cartilage; Morphogenesis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
MSX1 Transcription Factor* / genetics
MSX1 Transcription Factor* / metabolism
Mandible
Mice
Morphogenesis / genetics
Signal Transduction
Tooth* / metabolism

Substances

MSX1 Transcription Factor
Msx1 protein, mouse