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Browsing by Author "Päivinen, Linda"

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  • Päivinen, Linda (2018)
    Forkhead box G1 protein (FOXG1) is a transcription repressor that participates in multiple signaling pathways. FOXG1 formerly known as Brain factor 1 (BF1) is known for its effects on neurogenesis. FOXG1 is also expressed in the neural crest cells (NCC’s), specifically in the facial NCC’s that form the craniofacial structures. The aim of this study was to investigate the role of FOXG1 in the craniofacial bone development in mice and this was conducted by using a mouse strain with the Foxg1-gene targeted by Cre-recombinase (Cre), which represents Foxg1 null allele. Using a combination of mouse genetics, gene expression analysis and skeletal analysis was used and a difference was seen between mutated Foxg1cre/cre-embryos (MT) and wild type Foxg1+/+-embryos (WT). Abnormalities were found in the frontal region of the skull and in the nasal bones of the Foxg1cre/cre-embryos. The frontal suture was seen to be star shaped and wider in the mutants and the suture persisted after the WT suture narrowed. The frontal bones and the nasal bones were narrower, and the skulls were smaller in the MT – embryos compared to WT littermates. To analyze whether alteration in cell proliferation could account for these malformations, EDU-stainings at key stages of calvarial development were performed, but no abnormalities were found. Foxg1-mRNA was detected in the forebrain but not in the developing frontal bone mesenchyme. This might indicate that the phenotype is caused due to abnormalities possible in forebrain – calvarial mesenchyme tissue-tissue interactions or earlier due to abnormalities in the NCC’s. Between embryonic ages 9.5-12.5 (E9.5-E12.5), abnormalities in the distribution of the NCC marker HNK1 were noted in the Foxg1cre/cre mutant mice compared to Foxg1+/+ wild type. The differences may go some way to explain the craniofacial phenotype in these mice.