4.8 Article

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

Journal

SCIENCE
Volume 368, Issue 6486, Pages 48-+

Publisher

AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.aba5960

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Funding

  1. NIH [R01 NS028478, 1R01NS091544]
  2. Program for Breakthrough Biomedical Research - Sandler Foundation
  3. Shurl and Kay Curci Foundation
  4. LoGlio Foundation
  5. Sontag Foundation
  6. VA grant [5I01 BX000252]

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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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