4.7 Article

Meis2 controls skeletal formation in the hyoid region

期刊

出版社

FRONTIERS MEDIA SA
DOI: 10.3389/fcell.2022.951063

关键词

Meis2; cartilage; hyoid bone; Hand2; PBX1; mesenchymal condensation

资金

  1. Czech Science Foundation
  2. Charles University Grant Agency [22-10660S]
  3. Czech Centre for Phenogenomics [1034120, 340321]
  4. Ministry of Education, Youth and Sports [LM2015040]
  5. European Regional Development Fund [OP VaVpI CZ.1.05/2.1.00/19.0395]
  6. MEYS [CZ.1.05/1.1.00/02.0109]
  7. RVO [LM2018129, CZ.02.1.01/0.0/0.0/18_046/0016045]
  8. [68378050-KAV-NPUI]

向作者/读者索取更多资源

This study presents a model for studying hyoid apparatus development and finds that the lack of Meis2 in mice leads to abnormal development of the hyoid apparatus. The loss of Meis2 results in abnormal mesenchymal condensations, ectopic cartilage and bone formation, and increased proliferation of cartilage precursors. The study also shows that the reduced expression of PBX1 and HAND2 is associated with the loss of Meis2. These findings are important for understanding the developmental mechanisms of the hyoid apparatus.
A vertebrate skull is composed of many skeletal elements which display enormous diversity of shapes. Cranial bone formation embodies a multitude of processes, i.e., epithelial-mesenchymal induction, mesenchymal condensation, and endochondral or intramembranous ossification. Molecular pathways determining complex architecture and growth of the cranial skeleton during embryogenesis are poorly understood. Here, we present a model of the hyoid apparatus development in Wnt1-Cre2-induced Meis2 conditional knock-out (cKO) mice. Meis2 cKO embryos develop an aberrant hyoid apparatus-a complete skeletal chain from the base of the neurocranium to lesser horns of the hyoid, resembling extreme human pathologies of the hyoid-larynx region. We examined key stages of hyoid skeletogenesis to obtain a complex image of the hyoid apparatus formation. Lack of Meis2 resulted in ectopic loci of mesenchymal condensations, ectopic cartilage and bone formation, disinhibition of skeletogenesis, and elevated proliferation of cartilage precursors. We presume that all these mechanisms contribute to formation of the aberrant skeletal chain in the hyoid region. Moreover, Meis2 cKO embryos exhibit severely reduced expression of PBX1 and HAND2 in the hyoid region. Altogether, MEIS2 in conjunction with PBX1 and HAND2 affects mesenchymal condensation, specification and proliferation of cartilage precursors to ensure development of the anatomically correct hyoid apparatus.

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