title: Jam1a-Jam2a interactions regulate haematopoietic stem cell fate through Notch signalling.
abstract: Notch signalling plays a key role in the generation of haematopoietic stem cells (HSCs) during vertebrate development 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 specification. 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.
authors.affiliation: Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, California 92093-0380, USA.
authors.forename: Isao
authors.initials: I
authors.lastname: Kobayashi
authors.affiliation: Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, California 92093-0380, USA.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Kobayashi-Sun
authors.affiliation: Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, California 92093-0380, USA.
authors.forename: Albert D
authors.initials: AD
authors.lastname: Kim
authors.affiliation: Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, California 92093-0380, USA.
authors.forename: Claire
authors.initials: C
authors.lastname: Pouget
authors.affiliation: Section of Cell and Developmental Biology, University of California, San Diego, La Jolla, California 92093-0380, USA.
authors.forename: Naonobu
authors.initials: N
authors.lastname: Fujita
authors.affiliation: Department of Cell Differentiation, The Sakaguchi Laboratory, School of Medicine, Keio University, Shinjukuku, Tokyo 160-8582, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Suda
authors.affiliation: 1] Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, California 92093-0380, USA [2] Section of Cell and Developmental Biology, University of California, San Diego, La Jolla, California 92093-0380, USA.
authors.forename: David
authors.initials: D
authors.lastname: Traver
mesh_terms: D000818:Animals; D001011:Aorta / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D002454:Cell Differentiation; D002465:Cell Movement; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism*; D062745:Junctional Adhesion Molecule A / Q000235:genetics / Q000378:metabolism*; D062765:Junctional Adhesion Molecule B / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D051880:Receptors, Notch / Q000378:metabolism*; D015398:Signal Transduction; D019170:Somites / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D015027:Zebrafish / Q000196:embryology / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C571343:Jam2a protein, zebrafish; D062745:Junctional Adhesion Molecule A; D062765:Junctional Adhesion Molecule B; D011956:Receptors, Cell Surface; D051880:Receptors, Notch; D029961:Zebrafish Proteins; C000591481:f11r.1 protein, zebrafish