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Role of the noncanonical Wnt pathway in craniofacial development
Burianová, Andrea ; Machoň, Ondřej (advisor) ; Soukup, Vladimír (referee)
The craniofacial region, a complex structure defining the vertebrate head, results from intricate cellular and molecular processes governed by various genetic regulations and signaling cascades, including the noncanonical Wnt pathway. Dysregulations in this pathway, particularly involving Wnt5a, have been linked to craniofacial malformations, as seen in conditions like Robinow syndrome. This study aimed to elucidate the role of Wnt5a signaling in craniofacial development using mice with targeted deletion of Wnt5a specifically in the neural crest cells, which give rise to craniofacial structures. Our findings highlight the critical involvement of Wnt5a in shaping craniofacial precartilage condensations and regulating cellular behaviors such as proliferation, oriented cell division, and primary cilia polarity during early craniofacial morphogenesis. Wnt5a signaling is also important for key developmental populations, such as Msx1+ and Pax3+ populations. These findings not only contribute to the current understanding of noncanonical Wnt signaling in craniofacial development but also offer valuable insights into the intricate regulatory networks governing this process. Keywords: Wnt5a signaling, neural crest cells, morphogenesis
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Development of neural crest cells in zebrafish Danio rerio
Psutková, Viktorie ; Machoň, Ondřej (advisor) ; Fabian, Peter (referee) ; Svoboda, Ondřej (referee)
The neural crest is a population of migrating cells found only in vertebrates. Neural crest cells migrate to the head, heart and trunk regions of the body where they transform into different cell types. The cranial neural crest cells differentiate into chondrocytes and tenocytes, among others. The chondrogenic property of the cranial neural crest has given the vertebrates an advantage during evolution. In this paper, we focus on specific functions of the cranial neural crest and its derivatives in zebrafish (Danio rerio). The migration streams of the cranial neural crest follow the antero-posterior axis which is set up by hox genes. The development of the neural crest is controlled by a vast gene regulatory network. Here, we focus on the meis genes within the craniofacial development of zebrafish. For analysis, we used knock out (KO) mutant lines for each paralog of the meis gene (meis1a, meis1b, meis2a, meis2b). Only the meis1b KO and double meis1a1b KO mutants exhibit malformatins of the cranial cartilages, derivatives of the neural crest. We identified changes during cartilage formation. However, the migration of the neural crest into the pharyngeal arches and subsequent chondrocyte condensation remained unchanged. The formation of the facial part of the skull, so-called viscerocranium, is the...
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Genetic regulation of the cranial cartilage and bone development
Burianová, Andrea ; Machoň, Ondřej (advisor) ; Kaucká, Markéta (referee)
The skull development is an elaborate sequence of cellular processes, featuring two distinct tissue lineages, a unique transient pluripotent population of neural crest cells and mesodermal cells. Several differences in molecular mechanisms operating during chondrogenesis and skeletogenesis have been demonstrated in cranial bones originating from these different cell lineages. The bones comprising the cranial skeleton are formed through both intramembranous and endochondral ossification, regardless of the origin. The cellular processes involved in the formation of cranial skeletal elements include induction, migration, condensation, differentiation, and proliferation, all of which require sophisticated genetic control. Recent discoveries provide evidence of several signaling pathways and their target genes contributing to cranial skeleton development. The interconnection between individual signaling cascades is extremely complex and creates an entire gene regulatory network. This thesis focuses primarily on genetic programmes controlling the development of neural crest-derived skeletal structures. Keywords: neural crest cells, osteogenesis, chondrogenesis, mesenchymal condensation, gene regulatory network
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Role of transcription factors Meis during embryogenesis Danio rerio
Brežinová, Veronika ; Machoň, Ondřej (advisor) ; Krylov, Vladimír (referee)
Meis transcription factors belong to the group of TALE (three amino acids loop extension) homeodomain proteins. Meis2 proteins have a potential role in regulation of neural crest cells development and in differentiation of their derivates. Zebrafish genome has two paralogues of meis2 gene, meis2a and meis2b. CRISPR/Cas9 technology was used to prepare mutant lines of both paralogues, meis2a and meis2b, for the purpose of study of function of Meis2 transcription factors. Specific morpholinos that reduce the expression of meis2a and meis2b were used as controls. Craniofacial and cardiac development in mutant fish was analyzed in the meis2a line by RNA in situ hybridization, histological cartilage staining, and computed tomography. While we observed impaired craniofacial and cardiac development after injection of specific Morpholinos, we did not detect similar changes in the meis2a KO line. Our genetic approach has not clearly shown that the meis2a paralogue itself plays an important role in craniofacial development and cardiac development. For more detailed analysis, further experiments on fish lines with combined meis2a and meis2b knock-outs are needed. Key words Mutagenesis CRISPR, Danio rerio, neural crest cells, Meis2, transcription factor
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