Identification of lineage restricted precursor cells
The concept of progressive lineage restriction is well accepted for hematopoeisis but has not been established in such detail in the developing CNS. We are pursuing how lineage restriction is regulated in various brain regions of the CNS. For example, we have discovered that embryonic glial precursor cells do not directly generate terminally differentiated cell types, but give rise to other, more restricted precursor cell types before terminal differentiation (see Figure 1) (i.e. Herrera J, et al, Exp Neurol. 2001; Rao MS, et al, Proc Natl Acad Sci U S A. 1998; Mayer-Proschel M, et al Neuron 1997; Gregori et al, 2002, J. Neurosci.). Moreover, we showed that specification of postnatal oligodendrocyte precursor cells in tissues as closely related as optic nerve and optic chiasm is distinct in that glial precursor cells derived from the different regions of the brain respond in different ways to their environment (Mayer-Proschel et al 2002 Dev. Biol). We have extended our investigations of precursor cell populations to the developing cortex, one of the most complex tissues in the brain and could again identify and characterize a precursor cell pool that is restricted to the glial lineage (Strathmann et al, BMC Dev Biol. 2007). The identification of these different cell pools is critical for identifying ideal transplantable cells for therapeutic cell replacement approaches.
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