| The adult human neocortex is a complex structure, comprised of approximately ten billion neurons that are essential for processing external inputs from the tactile, auditory, or visual senses and generating appropriate motor responses. In order to process information efficiently, the neocortex is organized along both the anterior-posterior and medial-lateral axes into areas as well as radially into layers. Individual cortical areas are necessary for processing and generating responses to input from a single sensory modality, while neurons within specific layers are devoted to receiving, processing, or relaying information between cortical areas and out of the neocortex. Patterning of the neocortex during development occurs first through the early activation of combinatorial codes of transcription factors in the progenitor cells by signaling molecules. Transcription factors then regulate the expression of downstream genes and ultimately provide the genetic information necessary for establishing neuronal identity within an area or layer.; This thesis explores the roles of two transcription factors, Fezl and Otx1, in laminar fate specification and the formation of cortical areas, respectively. Both of these genes are expressed by neurons in the deep layers 5 and 6 during development, but genetic analyses reveal that they play quite distinct roles. Through a detailed analysis of axonal projections and the expression patterns of layer specific molecular markers, we demonstrate that Fezl is required for the differentiation of subcortically projecting neurons in layer 5. While the analysis of the size and location of cortical areas in Otx1 mutants, revealed significant changes in cortical arealization characterized by a reduction in the size of posterior cortical areas while anterior areas remain relatively unaffected. These changes appear to result from a role for Otx1 in early regionalization of the anterior neural tube. Researchers have only begun to identify the transcription factors that are needed to generate the wide variety of neuronal subtypes that function within the adult neocortex. This work delineates novel roles for two more transcription factors necessary for normal cortical development. |
