The Role of NfiB in the Generation of Neural Progenitors and Cortical Projection Neurons in the Developing Cerebral Cortex

The cerebral cortex is the most developed part of the human brain and is responsible for sense perception and cognitive abilities.  It is organized into layers, each comprised of a predominant neuronal subtype. Laminar organization of the cerebral cortex reflects the sequential generation, or birthdate, of neurons with distinct morphological and connective identities. Cortical projection neurons are generated in an inside-out pattern: layer 6 neurons, including most corticothalamic neurons, are born early and occupy the deepest layer of the cortex, followed by layer 5 subcerebral and corticocortical projection neurons, while corticocortical projection neurons of layers 3 and 2 are born last (McConnell, 1995; O'Leary and Koester, 1993). Clearly, cortical projection neuron birthdate and subtype identity are tightly correlated with laminar position. Recent work has shown that specific transcription factor expression in cortical neurons is critical to determining neuronal cell fate (McKenna et al., 2011, Chen et al., 2008).  However, the molecular mechanisms underlying the temporal and spatial generation of neuronal subtypes from neural progenitors is poorly understood.  Here we investigated the role of Nuclear Factor One B (NfiB) in the cortical progenitor cells.  NfiB is expressed in neural progenitors and deep layer cortical neurons suggesting a role in cortical neurogenesis.  Using an NfiB-/- mouse line, we performed immunohistochemistry and quantitatively analyzed the effect of NfiB deletion on rates of neurogenesis, and on overall distribution of distinct neural progenitor populations throughout development.  Furthermore, we investigated the effects on the birthdates and migration patterns of individual neuronal subtypes.