The concept of progressive lineage restriction is well accepted for hematopoeisis but has not been established in such detail in the developing CNS. A major focus of the laboratory is to understand how lineage restriction is regulated in various brain regions of the CNS and how specific lineage restricted progenitor populations contribute to developmental processes. In this regard, our laboratory is responsible for discovery of 4 of the 6 lineage-restricted progenitor cells of the CNS that have been isolated from the animal, studied at the clonal level and studied by transplantation in vivo. The discovery of novel progenitor cells in the embryonic CNS has opened up multiple new avenues of research. For example, the collaboartive effort with the laboratories of Drs Davies (Colorado), Proschel and Noble, resulted in the discovery that embryonic glial-restricted precursor (GRP) cells can give rise to two distinct types of astrocytes that upon transplantation into a spinal cord injury model result in entirely different outcomes. While the astrocyte populations generated with the cytokine BMP promote complete functional recovery, astrocytes generated by exposure of GRP cells to CNTF provides no functional recovery but does cause neuropathic pain syndromes. The laboratory is now focusing on defining the optimal precursor cell populations for transplantation repair strategies that result in beneficial and predictable therapeutic outcomes and that eliminate the risk for causing more harm than benefit. Along with the identification of precursor cells and their suitability for therapeutic application, the laboratory is invested in understanding the developmental windows during which precursor cell function coincide with windows of vulnerability of the developing brain to many extrinsic insults. Defining these windows of vulnerability provides a critical foundation for understanding how disturbances of stem and progenitor cell function may contribute to human diseases.
Davies JE, Proschel C, Zhang N, Noble M, Mayer-Proschel M, Davies SJ. Transplanted astrocytes derived from BMP- or CNTF-treated glial-restricted precursors have opposite effects on recovery and allodynia after spinal cord injury.
J Biol. 2008 Sep 19;7(7):24. [Epub ahead of print]
Strathmann FG, Wang X, Mayer-Proschel M. Identification of two novel glial-restricted cell populations in the embryonic telencephalon arising from unique origins. BMC Dev Biol. 2007 Apr 17;7:33.
Davies JE, Huang C, Proschel C, Noble M, Mayer-Proschel M, Davies SJ. Astrocytes derived from glial-restricted precursors promote spinal cord repair. J Biol 2006; 5(3):7