Isolation and developmental characterization of cerebral cortical multipotent progenitors

Area of Science:

• Neuroscience
• Developmental Biology
• Cell Biology

Background:

• Multipotent neural progenitor cells are typically found in brain generative zones.
• Lineage specification was thought to be confined to these zones during development.

Purpose of the Study:

• To investigate the presence and characteristics of multipotent neural progenitor cells outside of generative zones in the postnatal cerebral cortex.
• To determine the differentiation potential and responsiveness to growth factors of these cortical progenitor cells.

Main Methods:

• Quantitative immunoselection to isolate polysialylated neural cell adhesion molecule (PSA-NCAM)-expressing progenitor cells from postnatal day 2 cerebral cortex.
• Proliferation assays in response to epidermal growth factor (EGF).
• Clonal analysis to assess differentiation into neurons, astrocytes, and oligodendrocytes.

Main Results:

• An enriched population of multipotent neural progenitor cells was isolated from the cerebral cortex, independent of generative zones.
• These cortical progenitor cells proliferated in response to EGF and generated neurons, astrocytes, and oligodendrocytes.
• Cortical multipotent cells uniformly expressed PSA-NCAM, unlike generative zone cells with mixed expression. Cortical progenitors responded to PDGF and NT-3, while primary oligodendroglial progenitors responded only to PDGF.

Conclusions:

• The cerebral cortex contains a distinct pool of multipotent progenitor cells capable of generating glial progeny in response to specific environmental cues.
• These findings suggest a novel therapeutic strategy for brain injury by targeting endogenous multipotent progenitor cell differentiation.