Publication Date:
2014-08-15
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4237229/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4237229/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kobayashi, Isao -- Kobayashi-Sun, Jingjing -- Kim, Albert D -- Pouget, Claire -- Fujita, Naonobu -- Suda, Toshio -- Traver, David -- R01 DK074482/DK/NIDDK NIH HHS/ -- R01-DK074482/DK/NIDDK NIH HHS/ -- England -- Nature. 2014 Aug 21;512(7514):319-23. doi: 10.1038/nature13623. Epub 2014 Aug 13.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, California 92093-0380, USA. ; Section of Cell and Developmental Biology, University of California, San Diego, La Jolla, California 92093-0380, USA. ; Department of Cell Differentiation, The Sakaguchi Laboratory, School of Medicine, Keio University, Shinjukuku, Tokyo 160-8582, Japan. ; 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.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25119047" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Aorta/cytology/growth & development/metabolism
;
Cell Differentiation
;
Cell Movement
;
Hematopoietic Stem Cells/*cytology/*metabolism
;
Junctional Adhesion Molecule A/genetics/*metabolism
;
Junctional Adhesion Molecule B/genetics/*metabolism
;
Phenotype
;
Receptors, Cell Surface/genetics/*metabolism
;
Receptors, Notch/*metabolism
;
*Signal Transduction
;
Somites/cytology/embryology/metabolism
;
Zebrafish/embryology/*metabolism
;
Zebrafish Proteins/genetics/*metabolism
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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