People / Roffler-Tarlov Laboratory

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Research Interests

Our current research aims to test the hypothesis that catecholamines function as developmental signals even outside the nervous systems in addition to their better-known functions as neurotransmitters.

We study the effects of lack of catecholamines in a tyrosine hydroxylase-null mutant mouse created by gene targeting.  This mutation disables the key enzyme for catecholamine synthesis.  These mutant mice reveal that catecholamines can be produced by an alternate pathway, that catechols are essential for normal development.  Specifically, norepinephrine is essential both for embryonic viability and for thriving after birth until weaning: after that dopamine is key. The TH-null mice also show  that dopamine has a role in the pattern formation of the striatum in brain, and that norepinephrine directs the ability of cholinergic sympathetic synapses to function.

Research Collaborations

• Dr. Maribel Rios, Dr. Bill Brunken & Dr. Rob Jackson, Tufts University
• Dr. Dona Chikaraishi, Duke University
• Dr. Carol Mason, Columbia University

Lab Members

	Herve Maurin - Master's student from Universite Louis Pasteur, Strasbourg
	Maria Bernal - Research Assistant from Universidad de Los Andes, Bogota

Chris Boyson - Summer Student from University of Connecticut

Selected Publications

Roffler-Tarlov, S., Tarlov, E., Brown, J.J.G., Stolarov, J., Alexiou, M., Chapman, D.L., and Papaioannou, V.E. (1996) Programmed cell death in the absence of c-Fos and c-Jun. Development 122:1-9.  

Roffler-Tarlov, S., Martin, B., Graybiel, A.M., and Kauer, J.S. (1996) Cell death in the midbrain of the murine mutation weaver. J. Neurosci. 16:1819-1826. 

Oo,T.F., Blazeski, R., Harrison, S.M.W., Henchcliffe, C., Mason, C.A., Roffler-Tarlov, S.K., and Burke, R.E. (1996) Neuron death in the substantia nigra of weaver mouse occurs late in development and is not apoptotic.  J. Neuroscience, 16(9):6134-6145. 

Harrison, S.M.W., and Roffler-Tarlov, S. (1998) Cell Death During Development of the Testis and Cerebellum in the Mutant Mouse Weaver. Developmental Biology 195:174-186. 

Schein, J. C., Hunter, D.D., and Roffler-Tarlov, S.K. (1998) Girk2 Expression in the Ventral Midbrain, Cerebellum, and Olfactory Bulb and its Possible Relationship to the Murine Mutation weaver, Developmental Biology 204:432-450.

Rios, M., Habecker, B., Sasaoka, T., Eisenhofer, G., Tian, H., Landis, S., Chikaraishi, D., and Roffler-Tarlov,S. (1999)  Catecholamine Synthesis is Mediated by Tyrosinase in the Absence of Tyrosine Hydroxylase. J. Neurosci. 19:3519-3526.

Schimmel, J. S., Crews, L., Roffler-Tarlov, S., and Chikaraishi, D. M. (1999)  4.5 Kb of the Rat Tyrosine Hydroxylase 5’ Flanking Sequence Directs Tissue Specific Expression and Contains Consensus Binding Sites for Multiple Transcription Factors. Molecular Brain Research 74:1-14.

Tian, H., Habecker, B., Gurtan, M. Guidry, G, Rios, M., Roffler-Tarlov, S., and Landis, S.C., (2000)  Catecholamines are required for the acquisition of secretory responsiveness by sweat glands.  J. Neurosci. 19:7362-7369.

Bornstein, S.R., Tian, H., Haidan, A., Bottner, A., Hiroi, N., Eisenhofer, G., McCann, S.M., Chrousos, G.P., and Roffler-Tarlov, S. (2000) Deletion of Tyrosine Hydroxylase Gene Reveals Functional Interdependence of Adrenocortical and Chromaffin Cell System in vivo. PNAS  97:14742-14747.

Roffler-Tarlov, S. and Rios, M. (2001) Catecholamines without Nervous Activity, in Handbook on Brain and Behaviour in Human Development, A. Gramsbergen and A. Kalverboer, Eds., Kluwer Academic Publishers, 165-184.

Peng, J., Wu, Z., Wu, Y., Stevenson, F.F., Hsu, M., Boonplueang, R., Roffler-Tarlov, S.K., and Anderson, J.K., (2002)  Inhibition of caspases protects weaver cerebellar granule cells from developmental apoptosis and improves behavioral phenotype. J Biol Chem.;277(46):44285-91.

Portbury, A.L., Chandra, R., McMillan, M.K., Groelle, M., Elias, A., Herlong, J.R., Rios, M., Roffler-Tarlov, S., and Chikaraishi, D.M., (2003) Catecholamines act at a B3-Like adrenergic receptor in the mouse embryo to maintain heart rate during hypoxia. Am J. Physiol. Heart Circ. Physiol. 284(6):H2069-77.

Eisenhofer, G., Tian, H., Holmes, C., Matsunaga, J., Roffler-Tarlov, S., and Hearing, V., (2003) Tyrosinase: a Developmentally-Specific Major Determinant of Peripheral Dopamine Production.  FASEB  J. 17 (10), 1248-55

Schein,J.C.,Wang, JKT, and Roffler-Tarlov S.K. .  (2005)  The Effect of Girk2wv on Neurite Growth, Protein Expression, and Viability in the CNS-Derived Neuronal Cell Line, CATH.A-differentiated, Neuroscience, 134; 21-32.

Rios, M., Lambe, E., Liu, R., Teillon, S., Liu, J., Akbarian, S., Roffler-Tarlov, S., Jaenisch, R., Aghajanian, G.  (2005) Conditional BDNF mutant mice have normal presynaptic serotonin system but marked 5-HT_2A deficits.  J. Neurobiology, in press.