Timed deletion of Twist1 in the limb bud reveals age-specific impacts on autopod and zeugopod patterning
| Autor: | Angelyn C. C. Hor, Patrick P.L. Tam, David A.F. Loebel, Heidi Bildsoe |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Organogenesis
Limb Development lcsh:Medicine Mice Conditional gene knockout Forelimb Basic Helix-Loop-Helix Transcription Factors Morphogenesis lcsh:Science Musculoskeletal System Mice Knockout Multidisciplinary Gene Expression Regulation Developmental Nuclear Proteins Anatomy Animal Models Up-Regulation Patched-1 Receptor medicine.anatomical_structure Phenotype Intercellular Signaling Peptides and Proteins Female HAND2 Limb morphogenesis Research Article Patched Receptors animal structures Limb Buds Embryonic Development Receptors Cell Surface Mouse Models Biology Research and Analysis Methods Limb bud Model Organisms medicine Genetics Limb development Animals Body Patterning Homeodomain Proteins Twist-Related Protein 1 lcsh:R Biology and Life Sciences Body Plan Organization Embryo Mammalian Zone of polarizing activity HOXD13 biology.protein lcsh:Q Gene Function Organism Development Transcription Factors Developmental Biology |
| Zdroj: | PLoS ONE, Vol 9, Iss 6, p e98945 (2014) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | Twist1 encodes a transcription factor that plays a vital role in limb development. We have used a tamoxifen-inducible Cre transgene, Ubc-CreERT2, to generate time-specific deletions of Twist1 by inducing Cre activity in mouse embryos at different ages from embryonic (E) day 9.5 onwards. A novel forelimb phenotype of supernumerary pre-axial digits and enlargement or partial duplication of the distal radius was observed when Cre activity was induced at E9.5. Gene expression analysis revealed significant upregulation of Hoxd10, Hoxd11 and Grem1 in the anterior half of the forelimb bud at E11.5. There is also localized upregulation of Ptch1, Hand2 and Hoxd13 at the site of ectopic digit formation, indicating a posterior molecular identity for the supernumerary digits. The specific skeletal phenotypes, which include duplication of digits and distal zeugopods but no overt posteriorization, differ from those of other Twist1 conditional knockout mutants. This outcome may be attributed to the deferment of Twist1 ablation to a later time frame of limb morphogenesis, which leads to the ectopic activation of posterior genes in the anterior tissues after the establishment of anterior-posterior anatomical identities in the forelimb bud. |
| Databáze: | OpenAIRE |
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