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

Area of Science:

• Developmental Biology
• Hematopoiesis
• Cell Signalling

Background:

• Notch signalling is crucial for hematopoietic stem cell (HSC) generation in vertebrates.
• Intercellular communication is vital for Notch signalling, but the specifics of HSC development remain unclear.
• Previous work identified somitic Notch ligands (Dlc, Dld) essential for HSC specification.

Purpose of the Study:

• To elucidate the mechanism and timing of Notch signal transduction during HSC emergence.
• To investigate the role of junctional adhesion molecules (JAMs) in mediating Notch signalling for HSC fate.
• To connect somitic Notch ligand requirements with later HSC emergence from the dorsal aorta.

Main Methods:

• Utilized zebrafish as a model organism.
• Investigated gene expression of JAMs (jam1a, jam2a) and Notch pathway components in HSC precursors.
• Performed loss-of-function studies for jam1a and jam2a.
• Used enforced Notch activation to assess rescue of HSCs in deficient embryos.

Main Results:

• HSC precursors express jam1a and migrate across the ventral somite, where Jam2a and Notch ligands are present.
• Loss of jam1a function resulted in impaired Notch signalling and a deficit of HSCs, without altering Notch ligand/receptor expression.
• Enforced Notch activation rescued HSCs in jam1a or jam2a deficient embryos, confirming JAMs' role in signal transduction.
• Identified that JAM-mediated Notch signalling occurs prior to dorsal aorta formation.

Conclusions:

• Jam1a-Jam2a interactions are essential for transducing Notch signals from somites to HSC precursors.
• This process occurs during the migration of vascular precursors across the ventral somite, preceding dorsal aorta development.
• JAMs play a critical role in establishing HSC fate through Notch signal facilitation.