Stem Cell Center, Yale: iPSC and neural induction
Research in our laboratory investigates how neurons acquire distinct identities and form precise connections in the developing cerebral cortex, a part of the brain involved in a variety of higher cognitive, emotional, sensory, and motor functions. We also study how these developmental processes have changed during evolution and in human disorders. We study these problems for primarily two reasons. The first reason is to explore what it is about our brain that makes us human. The most important distinction between humans and other species is largely thought to reside in the unique features of human brain development, especially the way in which intricate neuronal circuits of the cerebral cortex are wired. The second reason for this research is to understand why humans suffer from certain brain diseases. The emergence of intricate neuronal circuits has given us remarkable cognitive abilities, but may have also increased our susceptibility to disorders such as autism and schizophrenia.
An important element of our research is the integration of complementary approaches at the interface of developmental neurobiology, molecular biology, comparative genomics, and genetics. To achieve this, we combine
- Analyses of evolutionarily conserved developmental mechanisms using the genetically tractable mouse model
- Comparative analyses to identify human-specific features of brain development
- Genetic and molecular analyses of disorders of human cognitive development
- The emerging biology of autism spectrum disorders. State MW, Sestan N (2012) The emerging biology of autism spectrum disorders. Science 337, 1301-1303.
- Cis-regulatory control of corticospinal system development and evolution. Shim S, Kwan KY, Li M, Lefebvre V, Sestan N (2012) Cis-regulatory control of corticospinal system development and evolution. Nature 86, 74-79.
- Species-dependent post-transcriptional regulation of NOS1 by FMRP in the developing cerebral cortex Kwan KY, Lam MMS, Johnson MB, Dube U, Shim S, Rasin MR, Sousa AMM, Fertuzinhos S, Chen JG, Arellano JI, Chan DW, Pletikos M, Vasung L, Rowitch DH, Huang EJ, Schwartz ML, Willemsen R, Oostra BA, Rakic P, Heffer M, Kostovic I, Judas M, Sestan N (2012) Species-dependent post-transcriptional regulation of NOS1 by FMRP in the developing cerebral cortex. Cell 149, 895-911.
- Kang HY, Kawasawa YI, Cheng F, Zhu F, Xu X, Li M, Sousa AMM, Pletikos M, Meyer KA, Sedmak G, Guennel T, Shin Y, Johnson MB, Krsnik Z, Mayer S, Fertuzinhos S, Umlauf S, Lisgo SN, Vortmeyer A, Weinberger DR, Mane S, Hyde TM, Huttner A, Reimers M, Kleinman