Paola Arlotta,
Ph.D. |
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| Title |
Instructor |
| Phone |
(617) 726-9252 |
| Fax |
(617) 726-2310 |
| Email |
paola_arlotta@hms.harvard.edu |
| Location |
Massachusetts General Hospital- Main Campus
MGH-HMS Center for Nervous System Repair
50 Blossom Street, EDR-410
Boston, MA 02114
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Research Overview
Data from our lab demonstrate that new neurons
can be added to adult neocortical circuitry from
transplanted neural precursors or via manipulation
of endogenous precursors in situ. These data
indicate that cellular repair of damaged neocortex
may be possible, if we could understand the molecular
controls over these events. Given the heterogeneity
of neuronal phenotypes in cortex, and the complexity
of their synaptic connections, attempts to functionally
repair neocortical circuitry will require detailed
understanding of signals that control directed differentiation,
survival, and connectivity of specific neuronal subtypes.
Brad Molyneaux and I have begun to address
this issue, and have identified a series
of critical genes that control both the initial
specification and further development of
the clinically relevant class of corticospinal
motor neurons (CSMN) in vivo (Arlotta,
Molyneaux et al., Neuron , Jan 20,
2005 ) . These genes include largely uncharacterized
transcription factors that distinguish CSMN
from other related classes of cortical projection
neurons (e.g. callosal projection neurons
and corticotectal projection neurons). Most
importantly, we find that some of these genes
are functionally relevant to the development
of this specific neuronal subtype in vivo.
Loss-of-function studies in null-mutant mice
demonstrate that Ctip2, one of the
newly characterized CSMN-specific genes,
plays a critical role in the development
of CSMN axonal projections to the spinal
cord in vivo. In addition, functional
analysis of a second CSMN-specific gene from
our screen, Fezl, demonstrate that
this transcription factor is both required
for the initial specification of CSMN, which
are absent from Fezl null-mutant neocortex,
and necessary to induce progenitors to form
CSMN in vivo (Molyneaux, Arlotta et
al., Neuron, Sept 15, 2005).
Understanding the signals that control
directed differentiation of CSMN in vivo is
central to the long-term goal of guiding
neural progenitors through the precise stages
of progressive and lineage restricted differentiation
that should be recapitulated to form CSMN
for therapeutic applications.
Key Recent Publications
- Arlotta, P. and Macklis, J.D. Archeo-Cell Biology: Carbon Dating is not just for Pots and Dinosaurs. Preview. Cell, 2005 15;122(1):4-6.
- Molyneaux B.J.*, Arlotta P*, Hirata T, Hibi M, Macklis JD. Fezl is required for the birth and specification of corticospinal motor neurons. Neuron, 2005 15;47(6):817-31 (*equal contribution). pdf
- 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. (*equal contribution). pdf
- Mitchell, B.D., Emsley, J.G., Magavi, S.S., Arlotta, P., and Macklis, J.D. Constitutive and induced neurogenesis in the adult mammalian brain: manipulation of endogenous precursors toward CNS repair. Dev Neurosci, 2004 26(2-4):101-17.
- Emsley, J.G., Mitchell, B.D., Magavi, S.S., Arlotta, P., Macklis, J.D.The Repair of Complex Neuronal Circuitry by Transplanted and Endogenous Precursors. Neurorx, 2004 1(4):452-471.
- Emsley, G.J.*, Arlotta, P.*,and Macklis, J.D. Star-cross’d Neurons: Astroglia Effects on Neural Repair in the Adult mammalian CNS. TINS 2004;27(5):238-40 . (*equal contribution).
- Catapano, L.A., Arlotta,P., Cage, T.A., and Macklis, J.D. Stage-specific and Opposing Roles of BDNF, NT-3, and bFGF in Differentiation of Purified Callosal Projection Neurons toward Cellular Repair of Complex Circuitry Eur. J. Neurosci. 2004;19(9):2421-34.
- Arlotta, P., Magavi, S.S. and Macklis, J.D. Induction of adult cortical neurogenesis from endogenous neural precursors. Annals of the New York Academy of Sciences. 2003;991:229-36.
- Arlotta, P., Magavi, S.S. and Macklis, J.D. Molecular manipulation of neural precursors in situ: induction of adult cortical neurogenesis. Exp. Gerontol. 2003;38:173-82.
Previous Publications
- Arlotta, P., Miyazaki, D., Copeland, N.G., Gilbert, D.J., Jenkins, N.A., and Ono, S.J. Murine NFX.1, isolation/characterisation of its messenger RNA, mapping of its chromosomal location and assessment of its developmental expression. Immunology. 2002;106(2):173-81.
- Liu, F., Chau, K.Y., Arlotta, P. and Ono, S.J. The HMG I proteins: dynamic roles in gene activation, development, and tumorigenesis. Immunol Res. 2001;24(1):13-29.
- Fedoseyeva, E.V., Boisgerault, F., Anosova, N.G., Wollish, S., Arlotta, P., Jensen, P.E., Ono, S.J. and Benichou, G.CD4 + T cell responses to self-P53 determinants during tumorigenesis in mice. J.Immunology. 2000;164(11):5641-51.
- Arlotta P., Tai, A., Manfioletti, G., Clifford, C.B., Jay, G. and Ono, S.J. Transgenic Mice Expressing a Truncated Form of the High Mobility Group I-C Protein Develop Adiposity and an Abnormally High Prevalence of Lipomas. J. Biol. Chem. 2000;275 (19):14394-400.
- Arlotta, P.*, Chau, K.Y.*, Patel, U., Crane-Robinson, C., Manfioletti, G. and Ono, S.J. A Novel downstream positive Regulatory Element Mediating Transcription of the Human High Mobility Group (HMG) I-C Gene. FEBS Letter 1999 Sep 3;457(3):429-36. (*equal contribution)
- Arlotta, P., Rustighi, A., Mantovani, F., Manfioletti, G., Giancotti, V., Tell G., and Damante, G. High mobility group I proteins interfere with the homeodomains binding to DNA. J. Biol. Chem. 1997 Nov 21;272(47):29904-29910.
Book Chapters
- Keane-Myers, A., Parry, C.S., Arlotta, P., Zhou, G., Radosevich, M., Chau, K.W., Tai, A.K.-F., Kreisberg, J.F., Chau, K.Y., and Ono, S.J. “Molecular Immunology of T-cells: Differential Cytokine Expression and Role in Allergic Disease”. Allergic Disease. M. Abelson editor. Allergan Press. 1997.
- Parry, C.S., Chau, K.Y., McParr, P., Zhou, G., Arlotta, P., Radosevich, M.D., Chau, K.W., Tai, A.K.-F.,Kreisberg, J.F., Manfioletti, G., Keane-Myers, A., and Ono, S.J. “B Lymphocyte Immunobiology, Molecular Genetics and Role in Atopic Disease”. Allergic Disease. M. Abelson editor. Allergan press. 1997.A.K.-F., Kreisberg, J.F., Chau, K.Y., and Ono, S.J. “Molecular Immunology of T-cells: Differential Cytokine Expression and Role in Allergic Disease”. Allergic Disease. M. Abelson editor. Allergan Press. 1997.
- Arlotta, P., Magavi, S.S. and Macklis, J.D. “Activation of Endogenous Neural Stem Cells”. Neural Stem Cells: Development and Transplantation. Kluwer Publishers. 2002.
- Arlotta, P., Magavi, S.S. and Macklis, J.D. Neurogenesis. McGraw-Hill Yearbook of Science & Technology 2003.
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