Research Tower
R325
675 Hoes Lane
Piscataway, NJ 08854

(732) 235-3471 (Office)
(732) 235-3409 (Lab)
(732) 235-4029 (FAX)
matisemp@umdnj.edu

Laboratory Home Page

My lab is interested in studying the mechanisms that control neuronal patterning and cell fate specification in the developing vertebrate spinal cord. We are currently focused on understanding 1) The function of the Gli zinc-finger transcription factors as mediators of Sonic hedgehog signaling, 2) The role of cell cycle and transcriptional regulators in neuronal cell cycle exit and differentiation, 3) The transcriptional determinants controlling neuronal patterning along the dorsoventral axis.

Our studies are guided by the principle that the developing embryo can best tell us what mechanisms are utilized to build a complex structure such as the central nervous system. Therefore we place a strong emphasis [on] in vivo approaches that allow us to preserve normal developmental contexts as much as possible. These approaches are technically challenging and sophisticated but are also unmatched in their power to identify and elucidate endogenous molecular mechanisms that control neural development. These approaches are complemented by anatomical, in vitro, biochemical and bioinformatic methods.

One of the central interests in my lab is understanding how neuronal patterning and identity is established during development. Our recent focus is on the role of the Gli transcription factors in this process. Three Gli proteins exist in vertebrates, Gli1, Gli2 and Gli3. These proteins are the primary mediators of the signaling pathway initiated by the secreted Sonic hedgehog (Shh) protein. We are currently engaged in studies to determine the individual transcriptional activities of the three Gli proteins. We are also interested in identifying target genes and genetic pathways regulated by these factors. Since defects in the Shh signaling pathway are associated with a growing number of human disorders and cancers, and since Gli proteins play a critical, central role in mediating Shh signaling, our studies are directly relevant to understanding the molecular mechanisms underlying cancers involving abnormal Shh pathway activation and will allow improved detection and treatment strategies to be designed.

Molecular genetic control of vertebrate CNS development

• Gene targeting in mouse ES cells
• Generation of transgenic mice
• In-situ gene and protein expression analysis
• Molecular cloning
• In-ovo electroporation in chick embryos
• Surgical tissue
  manipulations in chick embryos

For complete list: PubMed

Matise, M.P. (2002).
A dorsal elaboration in the spinal cord. Neuron 34, 491.

Wenner, P.W., O'Donovan, M.J. and Matise, M.P. (2001)
Topographical and physiological characterization of interneurons that express Engrailed-l in the embryonic chick spinal cord.
Journal of Neurophysiology 84, 2651.

Park, H.P., Bai, C., Platt, K.A., Matise, M.P., Beeghly, A., Hui, C., Nakashima, M. and Joyner, A.L. (2000)
Mouse Gli1 mutants are viable but have defects in Shh signaling in combination with a Gli2 mutation.
Development 127, 1593.

Matise, M.P., Lustig, M., Sakurai, T., Grumet, M. and Joyner, A.L. (1999)
Ventral midline cells are required for the local control of commissural axon guidance in the mouse spinal cord.
Development 126, 3649-3659.

Matise, M.P. and Joyner, A.L. (1999)
Gli genes in development and cancer.
Oncogene 18, 7852.

Matise, M.P., Auerbach, W. and Joyner, A.L. (1999)
Production of targeted embryonic stem cell clones.
In: Gene Targeting: A Practical Approach. Oxford Press.

Matise, M.P., Epstein, D.J., Park, H.L., Platt, K.P. and Joyner, A.L. (1998)
Gli2 is required for the induction of floor plate and adjacent cells, but not most ventral neurons in the mouse central nervous system.
Development 125, 2759.

Matise, M.P. and Joyner, A.L. (1997)
Expression patterns of developmental control genes in normal and Engrailed-1 mutant mouse spinal cord reveal early diversity in developing interneurons.
Journal of Neuroscience 17, 7805.