Research Article

Maintenance of neural stem cell positional identity by mixed-lineage leukemia 1

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Science  03 Apr 2020:
Vol. 368, Issue 6486, pp. 48-53
DOI: 10.1126/science.aba5960

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Sustaining stem cell identity

Stem cells in the developing brain acquire identities according to their locations and the types of neurons they will generate. As the brain grows larger and more complex, these identities must be maintained. Delgado et al. found this positional identity to be sustained by an epigenetic memory system. A morphogen sets the stem cell's identity early in development, but the identity is sustained by epigenetics.

Science, this issue p. 48

Abstract

Neural stem cells (NSCs) in the developing and postnatal brain have distinct positional identities that dictate the types of neurons they generate. Although morphogens initially establish NSC positional identity in the neural tube, it is unclear how such regional differences are maintained as the forebrain grows much larger and more anatomically complex. We found that the maintenance of NSC positional identity in the murine brain requires a mixed-lineage leukemia 1 (Mll1)–dependent epigenetic memory system. After establishment by sonic hedgehog, ventral NSC identity became independent of this morphogen. Even transient MLL1 inhibition caused a durable loss of ventral identity, resulting in the generation of neurons with the characteristics of dorsal NSCs in vivo. Thus, spatial information provided by morphogens can be transitioned to epigenetic mechanisms that maintain regionally distinct developmental programs in the forebrain.

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