Anthony-Samuel LaMantia, PhD
Professor

Education:

BS, University of Chicago, 1982
PhD, Yale University, 1988

Control of Gene Expression in the Developing and Adult Central Nervous System

There are two essential questions for understanding how neurons acquire and maintain their distinct properties. The first question is: How do undifferentiated embryonic epithelial cells establish an appropriate history of gene expression during development to define their identity as nerve cells in specific functional circuits? The second question is: What aspects of developmentally regulated gene expression must be retained or reactivated for mature neurons to adapt or change. To answer these questions we study how the steroid-like hormone Retinoic Acid (RA) controls gene expression in the developing and mature nervous system.

(click for description & larger image)

The central focus of the laboratory is understanding the role of RA-mediated signaling in the initial patterning and differentiation of the mammalian forebrain. We have shown that RA-mediated induction (a distinctive type of cell-cell signaling that occurs in embryos) guides the development of an entire functional subdivision of the forebrain, the olfactory bulb, as well as its primary source of innervation, the olfactory epithelium. We are now evaluating potential downstream target genes of early RA signals during forebrain development. We are also trying to define the roles of potential target genes in establishing neuronal identity, influencing axon guidance, determining target selection and patterning connectivity in the forebrain.

A second focus for the laboratory is understanding how RA-signaling in the adult nervous system acts to mediate neuronal plasticity and regeneration. We have found that RA mediated gene expression is retained at two well established sites of plasticity in the central nervous system. The first is in the olfactory epithelium where there is constant regeneration of primary sensory neurons, and the second is in the dorsal horn of the spinal cord where neurons modify there expression of a number of genes in response to peripheral injury or trauma. Both of these neuronal populations receive RA signals during development, and we are currently evaluating the role of continued RA-mediated gene expression for regeneration and plasticity in the adult.

Anthony LaMantia is co-author of Neuroscience (Sinauer & Associates, publisher), an introductory text of neurobiology for medical, graduate, and advanced undergraduate students.

References:

Balmer CW, LaMantia AS. (2004) Loss of Gli3 and Shh function disrupts olfactory axon trajectories. J Comp Neurol. 472(3):292-307.

Bhasin N, LaMantia AS, Lauder JM. (2004) Opposing regulation of cell proliferation by retinoic acid and the serotonin2B receptor in the mouse frontonasal mass. Anat Embryol (Berl). 208(2):135-43.

Miyamoto S, LaMantia AS, Duncan GE, Sullivan P, Gilmore JH, Lieberman JA. (2003) Recent advances in the neurobiology of schizophrenia. Mol Interv. 2003 (1):27-39. Review.

Maynard TM, Haskell GT, Peters AZ, Sikich L, Lieberman JA, LaMantia AS. (2003)
A comprehensive analysis of 22q11 gene expression in the developing and adult brain.
Proc Natl Acad Sci U S A. 100(24):14433-8.

Bhasin N, Maynard TM, Gallagher PA, LaMantia AS. (2003) Mesenchymal/epithelial regulation of retinoic acid signaling in the olfactory placode. Dev Biol. 261(1):82-98.

Maynard T.M., Haskell G.T., Bhasin N., Lee J., Gassman A.A., Leiberman J.A., and A.-S. LaMantia (2002). RanPB1, a velocardiofacial/ DiGeorge syndrome candidate gene, is expressed at sites of mesenchymal/epithelial induction. Mech. Of Devel. 111:177-180.

Maynard T.M., Jain M.D., Balmer C.W., and A.-S. LaMantia (2002). High resolution mapping of the Gli3 mutation Extra ToesJ reveals a 51.5kb deletion. Mammalian Genome 13:58-61.

Maynard TM, Haskell GT, Lieberman JA, LaMantia AS. (2002) 22q11 DS: genomic mechanisms and gene function in DiGeorge/velocardiofacial syndrome. Int J Dev Neurosci. 20(3-5):407-19.

Thompson Haskell G, Maynard TM, Shatzmiller RA, LaMantia AS. (2002) Retinoic acid signaling at sites of plasticity in the mature central nervous system. J Comp Neurol. 452(3):228-41.

Maynard T.M., Sikich L.M., Lieberman J.A., and A.-S. LaMantia (2001). Neural development, cell-cell signaling, and the two-hit hypothesis of schizophrenia. Schiz. Bull. 27:457-476.

LaMantia AS, Bhasin N, Rhodes K, Heemskerk J (2000) Mesenchymal/epithelial induction mediates olfactory pathway formation. Neuron 28(2):411-25.

Rubin WW, LaMantia AS. (1999) -dependent retinoic acid regulation of gene expression distinguishes the cervical, thoracic, lumbar, and sacral spinal cord regions during development. Dev Neurosci 21(2):113-25.

LaMantia AS. (1999) Forebrain induction, retinoic acid, and vulnerability to schizophrenia: insights from molecular and genetic analysis in developing mice. Biol Psychiatry 46(1):19-30.

Whitesides, J.G., Hall, M.E., Anchan, R.M., LaMantia, A.-S. (1998) Retinoid signaling distinguishes a subpopulation of olfactory receptor neurons in the developing and adult mouse. J. Comp. Neurol. 394:445-461.

Anchan, R.M., Drake, D.P., Gerwe, E.A., Haines, C.F., LaMantia, A.-S. (1997) Disruption of local retinoid-mediated gene expression accompanies abnormal development in the mammalian olfactory pathway. J. Comp Neurol. 379: 171-184.

Colbert, M.C., Rubin, W.W., Linney, E., and LaMantia, A-S. (1995) Retinoid signaling and the generation of regional and cellular diversity in the embryonic mouse spinal cord. Developmental Dynamics 204: 1-12.

LaMantia, A-S., Colbert, M.C., and Linney E. (1993) Retinoic acid induction and regional differentiation prefigure olfactory pathway formation in the mammalian forebrain. Neuron 10: 1035-1048.