Area of Research

Stem Cell Biology, Cell Specification & Differentiation, Neural Degeneration & Repair

Specialization

Glial differentiation in mammalian CNS development; progenitors in the adult CNS; cytoskeletal abnormalities and stress proteins in neurological disorders.

RESEARCH THEME

Research interests in our laboratory include developmentalneurobiology, particularly cell lineages and the regulation ofdevelopmental fates; the nature of progenitor cells in the adult CNS;and glial cell pathology in neurodegenerative disorders.

We are tracing celllineages in the developing mammalian CNS to study the origins ofastrocytes and oligodendrocytes from immature neuroectodermal cells.Using retroviral mediated gene transfer, we are following the migrationand differentiation of immature cells of germinal zones in vivo andhave determined that there are time- and location-specific patterns ofglial development. We are examining what roles environmental vs.lineage-controlled factors play in specifying cell fate. We are alsoinvestigating the nature of cycling cells in the adult mammalian CNSand characterizing their phenotypes and their fates under normal andpathological circumstances. For example, cycling, immature cells thatnormally do not differentiate are stimulated to develop intomyelinating oligodendrocytes after demyelination, thus contributing tothe repair of the lesion.

We are studyingglial reactions in pathological states, focusing upon specific proteinsof astrocytes. Particular interests include GFAP, the majorintermediate filament type in astrocytes, and the small heat shockprotein, alpha B-crystallin, expressed in glial cells normally, butupregulated in pathological conditions. Massive amounts of crystallineand GFAP accumulate in the brains of children with Alexander's disease,a fatal CNS degenerative disorder, caused by heterozygous pointmutations in GFAP. We have found that the accumulation of GFAP evokes acellular "stress" response and we are studying the molecular mechanismsby which this occurs.

SELECTED PUBLICATIONS

Marshall, CAG, Novitch, B, and Goldman,JE (2005). Olig2 directs astrocyte and oligodendrocyte formation inpostnatal SVZ cells. J.Neurosci., 25: 7289-7298.

MasonJL, Angelastro J, Greene L, Goldman, JE (2005). ATF5 regulates theproliferation and differentiation of oligodendrocytes. Mol. Cell.Neurosci., 29: 372-80.

Angelastro J, Mason JL, Goldman JE, Greene L(2005). Downregulation of ATF5 is required for differentiation ofneural progenitor cells into astrocytes. J. Neurosci., 25: 3889-3899.

Hsiao, VC, Tian, R,Long, H, Der Perng, M., Brenner, M, Quinlan, R., and Goldman, JE(2005). Alexander disease mutation of GFAP causes filamentdisorganization and decreased solubility of GFAP protein. J.Cell Sci.,118: 2057-2065.

Zerlin, MA, Milosevic, A., andGoldman, JE (2004). Glial progenitors of the neonatal subventricularzone differentiate asychronously, leading to spatial dispersion ofglial clones and to the persistence of immature glia in the adultmammalian CNS. Dev. Biol., 270: 200-213.

Mason,JL, Xuan, S, Dragatsis, I, Efstratiadis, A, and Goldman, JE (2003). IGFsignaling is important for remyelination in the adult CNS. J.Neurosci., 23: 7710-7718.

Suzuki, S and Goldman, JE (2003). Multiple cell populations in theearly postnatal SVZ take distinct migratory pathways: a dynamic studyof glial and neuronal progenitor migration. J. Neurosci., 23: 4240-4250.