The role of Hand2 in branchial arch and head-shoulder patterning.
Doctoral thesis, UCL (University College London).
Comprehending gnathostome evolution requires insights into key cellular and molecular components of craniofacial and shoulder development. For the work of this PhD, I made use of genetically modified mouse models to study aspects of mammalian head and shoulder morphogenesis by triple fluorescent RNA in situ hybridisation, immunohistochemistry and high resolution imaging. First- I use a genetically defined sentinel cell population labelled by the Hand2-Cre transgene to establish the expansion of the distal-most branchial arch domain and correlate this by triple fluorescent RNA in situ hybridisation with the system controlling proximo-distal branchial arch patterning, the Dlx system. I find that the axis of the Dlx system does not correspond to the proximo-distal but an endodermal-ectodermal axis of the arch and rotates during development; the overall expansion of the arch is explicable by telescopic outgrowth along this new axis. Second- I study the cellular and molecular characteristics of head/ shoulder skeleto-muscular connectivity and the contribution of limb lateral plate mesoderm to the shoulder girdle, which allows me to identify part of the manubrium sterni as the ‘lost’ mammalian procoracoid and to demonstrate that the interaction between lateral plate mesodermal subpopulations is non-random. Third- I establish novel roles for Hand2 in lower incisor ameloblasts and in laminar dermal bone formation, suggesting a fundamental role for Hand2 in epithelial and mesenchymal cell layer arrangements. My detailed study of the murine frontal bone reveals that the establishment of an internal and an external layer initiates dermal bone formation; the latter shows intermediate molecular periosteal/ perichondrial characteristics and generates the intermediate layer by a Hand2-dependent invagination process. For a comparative amphibian data set, I begin to establish genetic lineage labelling as technique in Xenopus tropicalis. I generate and test a Xenopus Hand2-Cre transgene and establish a stable generic Xenopus tropicalis Cre-reporter line by I-SceI mediated transgenesis.
|Title:||The role of Hand2 in branchial arch and head-shoulder patterning|
|Open access status:||An open access version is available from UCL Discovery|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Medical Sciences > Medicine (Division of) > Wolfson Inst for Biomedical Research|
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