We are interested in defining the molecular pathways that during development of the mammalian cerebral cortex direct the differentiation of neural progenitors/stem cells into distinct types of projection neurons, and the establishment of their interactions with inhibitory interneurons within the cortical microcircuitry.
We have a special focus on the early signals that induce differentiation of corticospinal neurons, a clinically relevant neuronal population that in humans selectively degenerates in ALS (Lou Gehrig's disease), Hereditary Spastic Paraplegia (HSP), Primary Lateral Sclerosis (PLS), and that is permanently injured in spinal cord injury (SCI).
During embryonic development, neural progenitors undergo precise differentiation to generate the amazing variety of neuronal types that ultimately populate the mature brain. While some of the basic mechanisms that control general aspects of progenitor specification into neurons have been defined, the molecular programs that control the differentiation of distinct types of neurons in the brain are only beginning to be understood. In our lab, we use molecular profiling methods to identify the key transcriptional, epigenetic and proteomic changes that govern corticospinal neuron specification and early stage differentiation during corticogenesis. A combination of experimental approaches including ultrasound guided injections in developing mouse embryos, in utero electroporation, and FACS purification of distinct neuron types are also applied to study the function of newly identified genes during development of corticospinal neurons.
Following the hypothesis that some of the same signals that control the birth and early development of corticospinal neurons during embryogenesis may be used to regenerate this neuron type in the mature brain, we are also investigating the possibility that pluripotent stem cells (i.e. iPS cells) may be directed to differentiate into corticospinal neurons for therapeutic application in neurodegenerative diseases of the corticospinal tract.
Dept. of Stem Cell and Regenerative Biology
7 Divinity Avenue, SF 358C
Cambridge, MA 02138