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Title: Foxg1 : a pleiotropic regulator of telencephalic development
Author: Martynoga, Ben
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2007
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This thesis focuses on the role of the forkhead box factor Foxg1 in the development of the vertebrate telencephalon. Mice mutant for Foxg1 exhibit multiple telencephalic defects demonstrative of an important pleiotropic role of rFoxg1 in telencephalic organogenesis. Severe hypoplasia of the null mutant telencephalon demonstrates that Foxg1 is required for the regulation of telencephalic growth. Experiments descried in this thesis provide the most systematic study to date of the mechanisms by which Foxg1 regulates this process. Broadly, the results demonstrate that Foxg1 is required to maintain progenitor cell fate, at the expense of differentiated cell fate, and to maintain the proliferation rate of progenitors. In addition to telencephalic growth defects, it has been documented that ventral telencephalic cell fates are lost in Foxg1-/- embryos. This thesis demonstrates that all ventral telencephalic lineages, which give rise to the basal ganglia and neuronal and glial constituents of the cerebral cortex, are completely absent in Foxg1-/- embryos. The requirement for Foxg1 to repress ectopic dorsal genes and to activate ventral genes is consistent with a role in regulating the response to ventralising signals. The hypothesis that Foxg1 is required for telencephalic cells to respond appropriately to the ventralising morphogen Shh is advanced. Evidence is provided for a role of Foxg1 in the regulation of the expression and activity of Gli3, the major antagonist of the hedgehog signalling pathway. In Foxg1-/-; Gli3-/- telencephalon, some aspects of ventral telencephalic fate are recovered. This demonstrates that Foxg1 is required for ventral fate specification, in part through the antagonism of Gli3 action, consistent with the original hypothesis. However, markers of ventro-medial telencephalic fate are not recovered and ectopic expression of dorsal markers persists in double mutants. From these findings it is argued that Foxg1 has hedgehog-independent roles in dorso-ventral patterning of the telencephalon.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available