Title: Interneuron development in Down syndrome
Legend: We assessed different neuron populations in human postmortem adult DS and age-matched control superiortemporal gyrus through immunocytochemistry and design based stereology and show that a specific subtype of interneuron, calretinin+, is reduced in DS brain (A). Calretinin-positive interneurons develop from a specific population of progenitors in the caudal ganglionic eminence (CGE) during development that express the transcription factor COUPTFII. Using trisomy 21 (Ts21) induced pluripotent stem cells (iPSCs) as a system to model prenatal interneuron development, we find that COUPTFII expression is reduced and the population of COUPTFII progenitors is reduced (B).
Citation: Giffin-Rao Y, Tao Y, Medo M, Strand B, Dantinne S, Keshan A, Daley R, Levesque B, Amundson L, Huang L, Reese R, Zhang SC, Bhattacharyya A. Interneuron development in Down syndrome, 6th Annual Cambridge Stem Cell Symposium, Spetember 2018.
Abstract: Neuropathology of the Down syndrome cerebral cortex includes fewer interneurons in upper cortical layers. Using Ts21 iPSCs tomodel cortical interneuron development in DS, we investigate missteps in their development that may lead to lack of interneurons in the adult DS brainOur results show that Ts21 interneuron progenitors have defects in patterning that alters interneuron subpopulations. Taken together, these data point to patterning defects in DS neural development that lead to altered interneuron generation. Understanding how mistakes in interneuron development in DS result in cognitive disability may enable us to intelligently design therapies to positively impact individuals and families living with DS.
About the Lab: Anita Bhattacharyya’s lab examines how brain development is altered in developmental disorders characterized by intellectual impairment. The cerebral cortex is the most complex area of the brain and is responsible for functions unique to humans, such as language and abstract thought. Problems in any of the crucial cerebral cortex formation steps can lead to intellectual impairment.