VEGF signaling is required for blastema growth and the effect of VEGF inhibition is reversible. (A) schematic of experimental design; (B) representative DMSO-treated limb at 11 dpa (scale bar 100 μm; arrowhead indicates blastema; dashed line indicates amputation plane); (C) representative AV951-treated limb at 11 dpa (scale bar 100 μm; arrowhead indicates blastema; dashed line indicates amputation plane); (D) AV951-treated blastemas are significantly smaller at 11dpa; (E) representative DMSO-treated limb at 22 dpa (scale bar 100 μm); (F) representative AV951-treated limb at 22 dpa (scale bar 100 μm; arrowhead indicates blastema); (G) AV951-treated limbs show no regeneration at 22 dpa; (H) skeletal prep of representative DMSO-treated limb at 22 dpa (scale bar 250 μm); (I) skeletal prep of representative AV95-treated limb at 22 dpa (scale bar 250 μm); (J) AV951-treated blastemas display blocked regeneration compared to controls; (K) AV951-treated blastemas can develop to palette stage upon treatment removal

#DBfeature

VEGF signalling promotes blastema growth and proliferation of both vascular and non-vascular cells during axolotl limb regeneration

By Aaron Savage et al.

tinyurl.com/3xs4nffs

Looks cool! Looking forward to reading it.

Congratulations Shiv and team! Looking forward to reading it.

Way to go Donna!

I see @sharansurya.bsky.social, who contributed to this project with repeated generational elevated glucose exposure experiments, is now on bluesky!

...of starvation actually extends organismal lifespan. If hypoxia is too dramatic that would obviously cause death, but if you have a sufficient exposure to induce the stress response pathways it can be beneficial! In this case the worms sacrifice fertility and shunt nutrients towards living longer

Thanks a lot! I know it's a bit counter-intuitive, but often times exposure to low levels of stress can induce the stress response pathways and then organisms have a beneficial response (termed hormesis). It's a similar theory to how dietary restriction, a reduction of food but not to the point ..

to a changing enivornment. I think we've evolved such that stresses that are strong enough are then transmitted to the descendants to alert them that conditions are not ideal and they should prepare for the adverse environment. But they are plastic so the hope is that adverse ones can be overcome

In plants I'm unfortunately not as familiar with the literature but again I'd be surprised if a sudden loss of nutrients or sunlight wouldn't have some consequence if it went on for long enough. Epigenetics exists right at the interface between the environment and genetics so it allows us to adapt

Thanks very much! Yes I think that even a "brief" stress if dramatic enough can have transgenerational consequences. The best examples in people are with the Överkalix study but I'd be surprised if dramatic overfeeding and starvation events didn't have a transgenerational consequence.

Thanks very much Dana!

Thanks so much!

Thanks a lot Oded! Been a fun project to work on for sure

Thanks a lot Amy! It's been a super fun project for sure!

Thanks! It's been a fun project for sure!

This exciting story was spearheaded by Kathleen but she was helped by a number of people mostly not on bluesky including Ariel Telger, Gautam Sarkar, Sharan Surya, Hafiz Rothi, @mpmeers.bsky.social, and Simon Yuan Wang. 9/9

Really excited for the next steps of this project to further study whether transgenerational adaptation is universal to different environmental stresses, how conserved this is in other species, and what the precise molecular mechanism is for the transgenerational adaptation. 8/9

We also performed a directed screen and identified that depletion of the argonautes CSR-1 and HRDE-1 accelerated the transgenerational adaptation (2 generations instead of 4 for no fertility phenotype) and depletion of the H3K27 trimethylase PRC2 complex eliminated the worms ability to adapt 7/9

..is not unique to hypoxia and might be a general phenomena. We performed RNAseq to examine which genes were adapting their expression to repeated generational hypoxia exposure. We found that most genes still respond to hypoxia treatment but a small subset adapt to repeated generational hypoxia 6/9

We also tested elevated glucose which increases neutral lipids and decreases fertility in exposed worms and unexposed descendants. After two successive exposures to elevated glucose neutral lipid levels and fertility were the same as unexposed controls.Therefore transgenerational adaptation..5/9

We found that after 2 successive generational exposures to hypoxia, worms were no longer long lived. After 4 successive generational exposures to hypoxia, worms no longer displayed a reduction in fertility. The worms adapted on a transgenerational scale to the repeated environmental stress! 4/9

Hypoxia induces transgenerational epigenetic inheritance of small RNAs - PubMed Animals sense and adapt to decreased oxygen availability, but whether and how hypoxia exposure in ancestors can elicit phenotypic consequences in normoxia-reared descendants are unclear. We show that hypoxia educes an intergenerational reduction in lipids and a transgenerational reduction in fertili …

We examined the effects of exposing successive generations to a stress we knew would induce epigenetic inheritance. Hypoxia exposure causes extended lifespan, reduced fertility, and reduced lipids and some of these phenotypes are heritable pubmed.ncbi.nlm.nih.gov/36516753/ 3/9

Recent work has demonstrated that a single exposure to a dramatic stress induces transgenerational phenotypes of altered color, obesity, glucose tolerance, behavior and longevity. But we are exposed to different environmental stresses each generation (changes in pesticides and fungicides etc) 2/9

Excited to share our new work on transgenerational adaptation www.science.org/doi/epdf/10.... out today spearheaded by outstanding former undergraduate @kathleenkim.bsky.social. C. elegans adapt to repeated generational stresses and no longer display altered fertility, fat content, + longevity 1/9

MADELEINE DEAN: The president is unhinged. He's unwell

JOHNSON: A lot of folks on your side are too

D: Oh my god, please. That performance in front of the generals?

J: I didn't see it

D: It's so dangerous! Our allies are looking elsewhere. Our enemies are laughing. You have a POTUS who's unwell.

Lysosomes signal through the epigenome to regulate longevity across generations The epigenome is sensitive to metabolic inputs and is crucial for aging. Lysosomes act as a signaling hub to sense metabolic cues and regulate longevity. We found that lysosomal metabolic pathways sig...

www.science.org/doi/10.1126/...

Just talked with my wife, we are cancelling our Disney+ subscription. If you have one, I encourage you to do the same.

Trump administration illegally froze billions in Harvard funds, judge rules The ruling is a legal victory for Harvard but the White House says it will appeal the decision.

A federal judge in Boston said she found it "difficult to conclude anything other than that [the Trump administration] used antisemitism as a smokescreen for a targeted, ideologically-motivated assault on this country's premier universities, and did so in a way that runs afoul of [federal law]."

Commentary: Hochul must sign bills that protect access to reproductive care As threats mount nationwide, New York must do all it can to ensure everyone can get the care they need.

Donna Lieberman of @nyclu.org is absolutely right. It's vital that @governor.ny.gov sign these critical bills to protect New Yorkers' reproductive freedom, including the NY Health Information Privacy Act that I carry w/@lindabrosenthal.bsky.social.
www.timesunion.com/opinion/arti...

Trump: "A lot of people are saying maybe we'd like a dictator."