On Wednesday 27 April 2011 Ms Sharon Mason, of the Cortical Development and Axon Guidance Laboratory at The University of Queensland's Queensland Brain Institute, will speak on the role of Nuclear Factor One (NFI) in cortical development.
Within the field of developmental neuroscience research remains a key question: how is the brain constructed normally during development? Understanding key cellular processes that construct the architectonic plan for the cortex and thereby, the foundation for early brain wiring events are critical to assist in our understanding of numerous human congenital syndromes. Human congenital cortical syndromes have defects in important basic cellular processes including neuron production, neuronal migration and neuronal maturation. These processes have similarities in both human and mouse. As a result of this, and the ease of genetic manipulation in the mouse, this model system is suitable to address many questions in mammalian corticogenesis. Members of Nuclear Factor One (NFI) transcription factor family comprising NFIA, NFIB, NFIC and NFIX have been identified as being highly expressed in the developing mouse brain. Within the mouse central nervous system (CNS), NFI transcription factors regulate the development of numerous CNS systems, including the spinal cord, basilar pons and hippocampus through regulating the differentiation of progenitor cells into neurons or glia. Additionally, NFI controls the post-mitotic development of cerebellar granule neurons.
In this thesis the role of the NFI gene family in the development of the mouse neocortex is investigated. The precise spatial and temporal protein expression of the NFIB family member during corticogenesis is described, with NFIB being detected in both progenitor and neuronal populations from early stages of neurogenesis. Given the expression pattern of NFIB, a main hypothesis of this thesis was that NFI may be involved in directing early neurogensis events within the neocortex. The cortical phenotype of the Nfib knockout mouse, compared to wildtype and Nfib heterozygous littermates was therefore characterised. This analysis demonstrated that NFIB is needed for the differentiation of basal progenitors. Defects in the timing of basal progenitor formation leads to delays in cortical plate lamination and axon outgrowth in the nascent cortex, including a disruption in the formation of the corticofugal and thalamocortical tracts. The defects are dependent upon the amount of NFIB in the system, as Nfib heterozygous mice demonstrate an intermediate phenotype.
Given the early defects in neurogenesis in Nfib-deficient mice, the radial glial population of the neocortex was characterised. Deficiencies were identified in radial glial differentiation. In correlation with this data, it was also shown that over-expression of Nfib in the neocortex in vivo caused precocious radial glial cell differentiation. Furthermore, microarray gene expression profiling in Nfib knockout cortices compared to wildtype revealed that genes in the notch pathway, cell cycle regulators, and molecules involved in axon outgrowth and basal progenitor formation were mis-regulated in the absence of NFIB.
Finally, NFIB was expressed in a high caudomedial to low rostrolateral gradient within the pseudostratified ventricular epithelium, and in the Nfib knockout mice, the transverse cortical maturation gradient was delayed, demonstrating that NFIB contributes to the cortical maturation gradient in normal development. Collectively, the expression, cellular and molecular data suggests that NFIB is required for the differentiation of radial glial cells within the neocortex, and in the absence of NFIB, the radial glial cells are immature and exhibit marked delays in their neurogenic competence.
Time: 12:00 - 1:00PM
Location: Level 7 Auditorium, QBI Building (#79), St.Lucia Campus
Seminars will be followed by a sandwich lunch for all attendees.
For a list of upcoming seminars at QBI, go to www.qbi.uq.edu.au/neuroscience-seminars.