Bhlha9 regulates apical ectodermal ridge formation during limb development
| Autor: | Kensuke Kataoka, Tempei Sato, Shigetoshi Yokoyama, Yoshiaki Ito, Takahide Matsushima, Hiroshi Asahara |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Apical ectodermal ridge Pathology medicine.medical_specialty Fibroblast Growth Factor 8 Endocrinology Diabetes and Metabolism Biology Article 03 medical and health sciences Limb bud Endocrinology Ectoderm TP63 Gene expression Basic Helix-Loop-Helix Transcription Factors medicine Animals Humans Limb development Orthopedics and Sports Medicine Syndactyly Apical ectodermal ridge formation Gene Mice Knockout Gene Expression Regulation Developmental Extremities General Medicine Phosphoproteins medicine.disease Cell biology Mice Inbred C57BL body regions Phenotype 030104 developmental biology Trans-Activators HeLa Cells |
| Zdroj: | Journal of Bone and Mineral Metabolism. 36:64-72 |
| ISSN: | 1435-5604 0914-8779 |
| DOI: | 10.1007/s00774-017-0820-0 |
| Popis: | Split hand/foot malformation (SHFM) and SHFM combined with long-bone deficiency (SHFLD) are congenital dysgeneses of the limb. Although six different loci/mutations (SHFM1-SHFM6) have been found from studies on families with SHFM, the causes and associated pathogenic mechanisms for a large number of patients remain unidentified. On the basis of the identification of a duplicated gene region involving BHLHA9 in some affected families, BHLHA9 was identified as a novel SHFM/SHFLD-related gene. Although Bhlha9 is predicted to participate in limb development as a transcription factor, its precise function is unclear. Therefore, to study its physiological function, we generated a Bhlha9-knockout mouse and investigated gene expression and the associated phenotype in the limb bud. Bhlha9-knockout mice showed syndactyly and poliosis in the limb. Moreover, some apical ectodermal ridge (AER) formation related genes, including Trp63, exhibited an aberrant expression pattern in the limb bud of Bhlha9-knockout mice; TP63 (Trp63) was regulated by Bhlha9 on the basis of in vitro analysis. These observations suggest that Bhlha9 regulates AER formation during limb/finger development by regulating the expression of some AER-formation-related genes and abnormal expression of Bhlha9 leads to SHFM and SHFLD via dysregulation of AER formation and associated gene expression. |
| Databáze: | OpenAIRE |
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