This is big one.
I am extremely pleased to (finally) be able to announce the publication of our most recent paper “Laminin N-terminus a31 expression during development is lethal and causes widespread tissue-specific defects in a transgenic mouse model” in FASEB Journal.
It has been a long journey to get this one over the line, but now it is out. It was worth the wait.
This is an important step forward in laminin research. It describes the first ever functional analyses of a LaNt protein in animals. The results demonstrate that this comparatively unstudied laminin and netrin-related protein is extremely potent, particularly in regulating blood vessel leakiness.
Before this study, work on the laminin N terminus (LaNt) family of proteins involved either observation of expression in human tissues or cancers or manipulation of LaNt expression in skin, corneal, or breast cancer cells in a dish. Those combined works have indicated that LaNt expression is increased in times of tissue remodelling and that LaNt is capable of influencing cell behaviours including cell migration and tumour invasion. However, the big caveat ofthese in vitro studies is that cells does not reflect the true complexity. The LaNt part of the laminin field is still quite small, and, quite simply, whether or not it is important or even functional in a whole organism was not yet known.
The findings in this paper therefore legitimately change the landscape of laminin research. It establishes that LaNts aren’t just spurious by products but rather are powerful regulators of tissue formation and function. When this new work is coupled to our prior studees on LaNt proteins, these effects on blood vessels are most likely via LaNt influencing basement membrane function through interaction with laminins.
This could change the way we think about context specific basement membrane remodelling and certainly warrants further investigation, particularly as earlier studies suggest roles in wound repair and cancer invasion.
An important part of the value of this paper to the field stems from some of the tools described therein. The new inducible line opens up numerous options now available for new studies. I am keen to collaborate in tissue and disease specific models, so please do check out the paper and share with your colleagues.
For non scientists, I’ve tried to capture the narrative journey that led up to this work (that we affectionately refer to as “LaNt wars”) available via this [link].