FGF-dependent Notch signaling maintains the spinal cord stem zone

Jun Akai, Pam A. Halley, Kate G. Storey

    Research output: Contribution to journalArticlepeer-review

    74 Citations (Scopus)

    Abstract

    Generation of the spinal cord relies on proliferation of undifferentiated cells located in a caudal stem zone. Although fibroblast growth factor (FGF) signaling is required to maintain this cell group, we do not know how it controls cell behavior in this context. Here we characterize an overlooked expression domain of the Notch ligand, Delta1, in the stem zone and demonstrate that this constitutes a proliferative cell group in which Notch signaling is active. We show that FGF signaling is required for expression of the proneural gene cash4 in the stem zone, which in turn induces Delta1. We further demonstrate that Notch signaling is required for cell proliferation within the stem zone; however, it does not regulate cell movement out of this region, nor is loss of Notch signaling sufficient to drive neuronal differentiation within this tissue. These data identify a novel role for the Notch pathway during vertebrate neurogenesis in which signaling between high Delta1-expressing cells maintains the neural precursor pool that generates the spinal cord. Our findings also suggest a mechanism for the establishment of the cell selection process, lateral inhibition: Mutual inhibition between Delta/Notch-expressing stem zone cells switches to single Delta1-presenting neurons as FGF activity declines in the newly formed neuroepithelium.
    Original languageEnglish
    Pages (from-to)2877-2887
    Number of pages11
    JournalGenes & Development
    Volume19
    Issue number23
    DOIs
    Publication statusPublished - 2005

    Keywords

    • Notch signaling
    • FGF signalling
    • Proneural genes
    • Spinal cord
    • Stem cells
    • Lateral inhibition

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