The Early Role of the Transcription Factor COUP-TFI in Cortical Development.

Teichmann, Hannah (2006). The Early Role of the Transcription Factor COUP-TFI in Cortical Development. MPhil thesis The Open University.



The mammalian neocortex is the seat of sensory and motor processing as well as higher brain functions. Its development is regulated by patterning centers and transcription factors expressed in temporally and spatially restricted fashions. Our understanding of the functions of such transcription factors during development has been limited by the pleiotropic effects and neonatal lethality resulting from null mutations. Chicken Ovalbumin Upstream Promoter Transcription Factor I (COUP-TFI) is a transcription factor expressed in the cortex during development, which has previously been implicated in cortical development by characterization of a COUP-TFI null mutant. In this report we described the use of a conditional mutant approach, in which COUP-TFI expression is eliminated exclusively from the cortex using lox-CRE technology, to investigate the role of COUP-TFI during cortical development. We have provided preliminary evidence for a novel role of COUP-TFI as a prodifferentiation factor in early cortical neurogenesis and as a regulator of neuronal diversity during the formation of the cortical plate. COUP-TFI appears to act as a regulator of upper versus lower layer neuronal cell fate in a way that is reminiscent of the function of its fly homolog, sevenup, in regulating early versus late neuronal fate in the fly nervous system. The elimination of COUP-TFI from the cortex also allowed us to identify its role outside of the cortex in guiding thalamocortical axons through the internal capsule. These data provide exciting prospects prospects for further insights into transcriptional programs regulating cortical development.

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