BBS Faculty Member - Paola Arlotta

Paola Arlotta

Department of Stem Cell and Regenerative Biology, Harvard University

Harvard University
Dept. of Stem Cell and Regenerative Biology
7 Divinity Avenue, SF 358C
Cambridge, MA 02138
Tel: 617 496-9810
Fax: 617 496-3763
Email: Paola_Arlotta@harvard.edu
Visit my lab page here.



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.

















Last Update: 8/9/2013



Publications

For a complete listing of publications click here.

 


 

Arlotta, P.*, Molyneaux, B.J.*, Chen, J., Inoue, J., Kominami, R. and Macklis, J.D. Neuronal Subtype-Specific Genes that Control Corticospinal Motor Neuron Development in vivo. Neuron 2005; 45 (2): 207-221.

Molyneaux, B.J.*,
Arlotta, P.*, Hirata, T., Hibi, M. and Macklis J.D. Fezl is Required for the Birth and Specification of Corticospinal Motor Neurons. Neuron 2005; 15;47(6):817-31.

Molyneaux, B.J.*,
Arlotta, P.*, Menezes, J. and Macklis J.D. Neuronal Subtype Specification in the Cerebral Cortex Nat. Rev. Neurosci. 2007; 8(6): 427-437.(*equal contribution)

Gao, X.,
Arlotta P., Macklis, J.D., Chen, J. Conditional knockout of b-catenin in newborn dentate gyrus granule neurons results in dendritic malformation in the postnatal hippocampus. The Journal of Neuroscience 2007; 27(52):14317-25.

Arlotta, P.*, Molyneaux, B.J.*, Jabaudon, D., Yoshida, Y. and Macklis J.D. CTIP2 Controls the Differentiation of Medium Spiny Neurons and the Establishment of the Cellular Architecture of the Striatum. The Journal of Neuroscience 2008; 16;28 (3):622-32. (*equal contribution)

Lai, T., Jabaudon, D., Molyneaux, B.J., Azim, E,
Arlotta, P., Menezes, J. and Macklis, J.D. SOX5 Controls the Sequential Generation of Distinct Corticofugal Neuron Subtypes. Neuron 2008; 57(2):232-247.

Rouaux C. and
Arlotta, P. Fezf2 Directs the Differentiation of Corticofugal Neurons from Striatal Progenitors in vivo. Nature Neuroscience. 2010; 13(11):1345-7. With “News and Views” article.

Zhang, F., Cong, L, Lodato, S., Kosuri, S. Church, G. and
Arlotta, P. Efficient Construction of Sequence-specific TAL Effectors for Modulating Mammalian Transcription. Nature Biotechnology. 2011; 29(2):149-153.

Lodato, S., Rouaux, C., Quast, K., Jantrachotechatchawan, C., Studer, M., Hensch, T. and
Arlotta, P. Excitatory Projection Neurons Control the Distribution of Inhibitory Interneurons in the Cerebral Cortex. Neuron. 2011; 69(4):763-79. With Previews article.



© 2013 by the President and Fellows of Harvard College