Jam1a-Jam2a interactions regulate haematopoietic stem cell fate through Notch signalling

Isao Kobayashi, Jingjing Kobayashi-Sun, Albert D. Kim, Claire Pouget, Naonobu Fujita, Toshio Suda, David Traver

    Research output: Contribution to journalArticle

    61 Citations (Scopus)

    Abstract

    Notch signalling plays a key role in the generation of haematopoietic stem cells (HSCs) during vertebrate development1-3 and requires intimate contact between signal-emitting and signal-receiving cells, although little is known regarding when, where and how these intercellular events occur. We previously reported that the somitic Notch ligands, Dlc and Dld, are essential for HSC specification4. It has remained unclear, however, how these somitic requirements are connected to the later emergence of HSCs from the dorsal aorta. Here we show in zebrafish that Notch signalling establishes HSC fate as their shared vascular precursors migrate across the ventral face of the somite and that junctional adhesion molecules (JAMs) mediate this required Notch signal transduction. HSC precursors express jam1a (also known as f11r) and migrate axially across the ventral somite, where Jam2a and the Notch ligands Dlc and Dld are expressed. Despite no alteration in the expression of Notch ligand or receptor genes, loss of function of jam1a led to loss of Notch signalling and loss of HSCs. Enforced activation of Notch in shared vascular precursors rescued HSCs in jam1a or jam2a deficient embryos. Together, these results indicate that Jam1a-Jam2a interactions facilitate the transduction of requisite Notch signals from the somite to the precursors of HSCs, and that these events occur well before formation of the dorsal aorta.

    Original languageEnglish
    Pages (from-to)319-323
    Number of pages5
    JournalNature
    Volume512
    Issue number7514
    DOIs
    Publication statusPublished - 2014 Aug 21

    ASJC Scopus subject areas

    • General

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