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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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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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