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Title: Temporal requirement of sonic hedgehog signaling during early craniofacial development
Author: Ahmadi Birjandi, Ana
ISNI:       0000 0004 8505 0292
Awarding Body: King's College London
Current Institution: King's College London (University of London)
Date of Award: 2018
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Sonic hedgehog (Shh) is a member of the Hedgehog family of signaling molecules, which govern many aspects of development and organogenesis. Shh is essential for normal formation of the forebrain and facial region and its absence leads to Holoprosencephaly (HPE), a developmental defect characterized by impaired cleavage of the forebrain and facial anomalies. This phenotype shows considerable heterogeneity and variation amongst individuals, which is not necessarily dependent upon genotype and emphasises the importance of appropriate control of Shh in the craniofacial region during development. Therefore the aim of this study was to investigate the relative contribution of Shh during early formation of the facial region with emphasis on the developing tooth and tongue using conditional mutant mice. Specifically, abrogating Shh signaling using a Tamoxifen-inducible ubiquitous Cre recombinase. The loss of Shh signaling from E7.5 results in a gross craniofacial phenotype indistinguishable from that of Shh mutant mice. Loss of signaling at later stages, E10.5-12.5 produced a range of phenotypes with a severity correlating with the timing of Shh signal loss. In the developing tooth, early loss of Shh resulted in only a very rudimentary bud, whereas loss of function at later stages allowed a rudimentary cap to form. In the tongue, loss of Shh function after the initiation of tongue development resulted in microglossia and formation of ectopic epithelial thickenings that resembled disorganized placodes. These thickenings later developed into bulb–like structures with disrupted morphology, innervation and delayed growth. In summary, these findings demonstrate a significant role for Shh signaling during early tooth and tongue formation through the regulation of epithelialmesenchymal interactions and the importance of understanding the temporal requirements of Shh signaling during the early stages of craniofacial development.
Supervisor: Cobourne, Martyn Timothy ; Liu, Karen Jasmine Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available