| Experiment Id | GSE146301 | Name | Axial skeleton anterior-posterior patterning is regulated through feedback regulation between Meis and retinoic acid |
| Experiment Type | RNA-Seq | Study Type | WT vs. Mutant |
| Source | GEO | Curation Date | 2023-02-08 |
| description | Vertebrate axial skeletal patterning is controlled by coordinated collinear expression of Hox genes and axial level-dependent activity of Hox protein combinations. Transcription factors of the Meis family act as cofactors of Hox proteins and profusely bind to Hox complex DNA, however their roles in mammalian axial patterning have not been established. Similarly, retinoic acid (RA) is known to regulate axial skeletal element identity through the transcriptional activity of its receptors, however whether this role is related to Meis/Hox regulation or functions in axial patterning remains unknown. Here we study the role of Meis factors in axial skeleton formation and its relationship to the RA pathway by characterizing Meis1, Meis2 and Raldh2 mutant mice. We report that Meis and Raldh2 regulate each other in a positive feedback regulatory loop that controls axial skeletal identity. Meis elimination produces homeotic transformations similar to those found in Raldh2 and anterior-Hox mutants and disrupts the expression of Hox target genes without changing the transcriptional profiles of Hox complexes. We propose that Meis regulates vertebrate axial skeleton patterning by exclusively affecting Hox protein function, and that alterations in RA levels can produce homeotic transformations without altering Hox transcription through regulating Meis expression. Transcriptomic analysis comparing control embryos to embryos mutant for Meis1 and Meis2 conditionally deleted using Delta1Cre. The aim was to identify Meis target genes involved in anterior-posterior skeletal patterning. To discriminate between early patterning effects and alterations during the somite differentiation phase, we separately analyzed the posterior axial bud together with the 10-12 newly formed somites and the rest of the embryonic axis, excluding the anterior regions devoid of somites. |
