Research Summary

Regulation of cortical stem cell chromatin by cortical selector gene Lhx2

The cerebral cortex is the most complex brain structure, involved in higher cognitive functions such as perception, language, learning and memory. Neurons, the basic functional unit of the brain, must be generated in the right numbers, locations and times, for the cortex to innervate and function correctly. We have identified Lhx2-LIM homeodomain transcription factor to be a selector gene which instructs cells in the developing brain to take on a cortical fate. Cells in which Lhx2 is expressed become cells of the cerebral cortex. Cells in which Lhx2 is not expressed cannot become cerebral cortex, but instead become a potent centre of molecular signals. These signals are critical to instruct surrounding cortical cells to develop into the hippocampus, a specialized cortical structure critical for learning and memory. Our research aims to understand the genetic pathways which Lhx2 regulates in neural epithelial precursor cells that enable them to take on a cortical fate. Loss of function, gain of function and biochemical approaches will be used to understand these mechanisms. Understanding this would provide a framework for normal brain development in the context of which the underlying mechanisms of disorders such as autism, epilepsy, and schizophrenia may be understood.

 

Figure Legend: Overexpression of Lhx2 (green) into the hippocampus at E17 causes neurogenesis from progenitors that would otherwise produce astrocytes. Embryos were electroproated in utero on the 17th day of gestation, and the brains were examined 5 days later (Subramanian et al., PNAS, 2011)