For
#FluorescenceFriday I'm sharing the fantastic work of postdoc Sarah McLarnon! A follow up to our '23 Development paper where we asked: Does precise vascular patterning matter for function and what happens after ischemic injury? The results were surprising!
journals.physiology.org/doi/full/10.... Jun 20, 2025 20:06In our 2023 paper we found that deletion of the guidance cue netrin-1 from stromal progenitors of the developing kidney leads to stochastic vascular patterning. We showed that the altered patterning persists in the adult kidney at 2-3 months of age, although other vascular metrics were similar.
We followed up the adults and investigated how the kidneys appear histologically and whether physiological function is altered. It all looks normal, for both males and females.
What about after a moderate acute ischemic injury? Are the kidneys with vascular mispatterning more susceptible? Surprisingly, the mistpatterned mutants of both sexes are better protected! There is less tubular injury and kidney function is improved.
Post-ischemia the vasculature appears comparable in both controls and mutants. No significant loss in density. The only visible difference is the mispatterning.
As vascular density can decrease with age, we looked at older animals. Interestingly, we found better preservation of perfused vasculature in the older mutant mice.
So how is the disrupted patterning protective and possibly more resilient? This is what we are following up on now. Story to be continued! Thanks to all the other lab members who contributed and a special thanks to our wonderful collaborator Tomo Souma and his team for helping assess injury.
This was a fun lesson in having your hypothesis proven wrong (we thought they would have worse outcomes after injury), and having that be even more exciting. We hope what we find may help inform tissue engineering and regenerative strategies, and lead to improved clinical interventions.