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Temporal fate specification and neural progenitor competence during development

Key Points

  • The vast neural diversity in the CNS is generated from a small pool of progenitors that produce distinct cell types in a specific order. The generation of a particular cell type depends on the spatial position of the progenitor (spatial patterning) as well as changing intrinsic and extrinsic signals (temporal patterning).

  • Neural progenitors sequentially express a series of transcription factors, which specify the fate of the progeny on the basis of birth timing (temporal identity). Distinct neural lineages can use the same temporal-identity factor to specify different progeny fates.

  • Distinct temporal-patterning cues in the neural progenitor and the progeny can act combinatorially to increase neural diversity.

  • Studies of neurogenesis in multiple organisms show that the molecular players involved in temporal fate specification are highly conserved.

  • In addition to the sequential specification of distinct cell fates, neural stem cells undergo dynamic changes in competence states, such that a given cell type can be specified during only a limited window of development. Thus, the specification of a particular cell fate requires the progenitor to be in the correct competence state to respond appropriately to the cell-fate-determining factors.

  • Emerging evidence indicates that global changes in chromatin architecture play an important part in the regulation of competence states.

Abstract

The vast diversity of neurons and glia of the CNS is generated from a small, heterogeneous population of progenitors that undergo transcriptional changes during development to sequentially specify distinct cell fates. Guided by cell-intrinsic and -extrinsic cues, invertebrate and mammalian neural progenitors carefully regulate when and how many of each cell type is produced, enabling the formation of functional neural circuits. Emerging evidence indicates that neural progenitors also undergo changes in global chromatin architecture, thereby restricting when a particular cell type can be generated. Studies of temporal-identity specification and progenitor competence can provide insight into how we could use neural progenitors to more effectively generate specific cell types for brain repair.

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Figure 1: Neurogenesis in ventral-nerve-cord neuroblast lineages in the Drosophila melanogaster embryo.
Figure 2: Neurogenesis in Drosophila melanogaster larval central-brain neuroblast lineages.
Figure 3: Temporal fate specification in mammalian retina.
Figure 4: Temporal fate specification in the mammalian cortex.
Figure 5: Reorganization of the neuroblast genome regulates competence transition in Drosophila melanogaster embryos.
Figure 6: Competence transitions during mammalian neurogenesis.

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Acknowledgements

The authors would like to thank S.-L. Lai and R. Galvao for helpful comments and suggestions. M.K. is supported by US National Institutes of Health (NIH) grant HD072035, and C.Q.D. is supported by NIH grant HD27056. C.Q.D. is an investigator of the Howard Hughes Medical Institute.

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Glossary

Neural progenitors

Multipotent progenitors that give rise to the diverse cell types of the CNS.

Asymmetric cell division

A mitotic division that generates daughter cells that have different cell fates.

Ganglion mother cell

(GMC). The differentiating daughter cell that is derived from the asymmetric division of a neuroblast. This cell will divide once more to generate two neurons or glia.

Cytokinesis

The final event in the cell-division cycle. Its completion results in the irreversible partition of a mother cell into two daughter cells. It involves cytoplasmic division driven by an actin-based constriction of the contractile ring.

MicroRNAs

Short, non-coding RNAs that inhibit translation of mRNAs in a sequence-specific manner.

Central complex

A region of the fly brain that is involved in multimodal sensory integration.

Nuclear lamina

A network of intermediate filaments and membrane-associated proteins of the nuclear envelope. Genes associated with the nuclear lamina compartment are often in a silenced or repressed state.

Polycomb repressive complexes

(PRCs). Multiprotein complexes that remodel chromatin to establish epigenetic silencing.

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Kohwi, M., Doe, C. Temporal fate specification and neural progenitor competence during development. Nat Rev Neurosci 14, 823–838 (2013). https://doi.org/10.1038/nrn3618

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