研究人員｜中央研究院 細胞與個體生物學研究所

The mammalian cerebral cortex is a remarkably complex organ responsible for the perception of sensory stimuli, the execution of motor actions, cognition and consciousness. It contains many neuronal cell types, and a substantial fraction of the more than 10 billion neurons in the human brain form 1013-1015 connections within the cortex and with other regions of the central nervous system. The generation of the variety of neuronal types and the establishment of proper connections are crucial for the function of cortex.

The cerebral cortex is comprised of several structural and functional domains, including the six-layered neocortex and the architecturally more simple and phylogenetically older cortices, including the paleocortex, which is predominantly the olfactory cortical structure, the piriform cortex; and the archicortex, which is predominantly the hippocampal formation. The neocortex is further patterned into specialized areas, including primary somatosensory, auditory and visual areas. Each of the primary sensory areas processes modality-specific sensory information relayed from the periphery via thalamocortical axon (TCA) inputs originating from the dorsal thalamus. Each of these functional domains in the cerebral cortex is characterized by unique cytoarchitecture, particular patterns of gene expression (as shown in Fig. 1), and specific sets of input and output processing networks.

The great majority of neurons that form each region of the cerebral cortex arise from one prominent continuous germinal zone, the ventricular zone in the dorsal telencephalon. Anatomically, the progenitors in the ventricular zone of the dorsal telencephalon appear uniform; however, they give rise to brain regions with different anatomies and neural connections. The fascinating question for us is how different cortical neurons are derived from the seemingly uniform progenitor population. It was shown previously that transcription factors that are expressed in graded patterns along the anterior-posterior and medial-lateral cortical axes control the location and size of primary sensory areas in the neocortex, and that TCA inputs play an instructive role in controlling area-specific gene expression.

The primary research interest of our laboratory is to understand the mechanisms controlling development of the cerebral cortex, with a particular focus on understanding how the uniform neuroepithelium of the embryonic dorsal telencephalon gives rise to specialized regions of the cortex (Fig. 2). Using a combination of genetic, embryological and molecular biology methods, we will explore how neuron diversity and the myriad of their connections are generated during development through the interplay of genetic programs intrinsic to the cortex and extrinsic mechanisms, such as neuronal inputs. Our long-term goals are to understand how changes in genes that regulate these processes lead to changes in cortical organization during evolution and disease.