Towards a blueprint for building the brain

S Tole

Tata Institute of Fundamental Research

The cerebral cortex arises from a simple sheet of neuroepithelial tissue in the embryo. How this sheet is patterned to produce distinct cortical structures in a reliable and reproducible manner is a question of both evolution and development. We discovered that the cortical hem, a Wnt-rich signaling center that forms at the telencephalic midline, acts as a secondary organizer in the embryonic brain, and induces the hippocampus. Embryos that were genetically manipulated to form additional ectopic hems displayed multiple ectopic hippocampi. How the hem itself forms and how its position is limited to the telencephalic midline therefore becomes a compelling question, because the position of the hem determines the position of the hippocampus. We explored interactions between three regulators of early patterning, transcription factors Foxg1, Lhx2, and Pax6, and identified mechanisms that regulate the formation and position of the cortical hem. These genetic interactions provide insight into the early steps of patterning of the cortical primordium. Further, we found that hem is itself part of a multi-component “forebrain hem system” that may have arisen as part of an evolutionary mechanism to regulate the formation of the cerebral cortex. Work in Dr. Tole’s lab has been supported by a Wellcome Trust Senior International Fellowship (056684/Z/99/Z), Swarnajayanti Fellowship (Dept. of Science and Technology, Govt. of India), and grants from the Department of Biotechnology, and the Department of Science and Technology, Govt. of India.