Neural Stem Cell Discovery Has Treatment Potential

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Transforming growth factor-beta may act as a switch-signal in the temporal patterning of the brain that executes the transition between early and late phases of neurogenesis, researchers have discovered.

The findings may provide a framework to modulate temporal identity and potency of neural cells in stem-cell engineering, which could lead to novel treatments for psychiatric and neurodegenerative diseases, according to Johan Ericson, PhD, of the Karolinska Institute in Stockholm, Sweden, and colleague.

Transforming growth factor-beta (TGF-beta) signaling executes the motor neuron (MN) to serotonergic neuron (5HTN) temporal fate switch in ventral hindbrain progenitors, the study findings showed. TGF-beta also suppressed early-born neuron and induced late-born cell types in different regions of the central nervous system.

Additionally, young Nkx2.2+ hindbrain progenitors can produce late-born 5HTN and that the timing of TGF-beta2 activation and execution of MN to 5HTN switch is intrinsically programmed within the Nkx2.2+ temporal lineage downstream of Sonic hedgehog (Shh), the researchers found.

This data suggests a novel “hierarchical dominance” model of sequential fate specification, where transcription factors promoting MN- and 5HTN-fate co-exist in young progenitors but where the activity of Phox2b predominates over 5HTN-fate determinants at early developmental stages.

Noting the important roles that 5HTNs play in psychiatric and neurodegenerative diseases, the results of this study suggest that extrinsic cues that regulate temporal neurogenesis can be used to bypass early phases, thus allowing stem cells to facilitate production of late-born and clinically relevant neurons.

Neuron
Neural Stem Cell Insights Offer New Treatment Avenues

New insights into how molecular time signaling controls stem cells at different stages of brain development could have implications for the development of novel treatments for psychiatric and neurodegenerative diseases, researchers reported.

Researchers from Karolinska Institute, in Stockholm, Sweden, discovered that TGF-beta acts as a switch-signal in temporal patterning of the vertebrate brain that executes the transition between early and late phases of neurogenesis.

The identification of TGF-beta as a temporal switch signal and regulator of neural progenitor potential provides a future framework to modulate temporal identity and potency of neural cells in stem-cell engineering.

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