Parichy Lab | Dave Parichy

Or the HR version with less Cormac McCarthy.

We have a postdoc position available. Please forward to anyone who may be interested.

Image of an adult male zebrafish (Danio rerio) with distinctive yellow and blue stripes. You can see their reflection in the bottom of the clear tank. Credit to Dr. Paco López-Cuevas.

Did you know @zebrafishhusbandry.bsky.social has a guide to zebrafish husbandry basics in 22 languages including Arabic, Cambodian, Chinese, Dutch, Farsi, French, German, Greek, Hindi, Italian, Serbian, Malay, Norwegian, Portuguese, Romanian, Russian, Spanish, Swahili, Turkish, Urdu & Japanese 1/2 🧪

YouTube video by University of Virginia UVA researchers look to songbirds to teach us about the human brain

Nice video for lay audience on use of songbirds for neurodegeneration/regeneration research, with UVA faculty member Dr. Tracy Larson (lab next door to mine and coPI of ongoing experiment to raise human F1s at home).

youtu.be/FUzuWyguADY?...

I called NC Senators Tillis and Budd--call your Senators!

Worth a read--the DEI scrubbing, while disappointing, is perhaps not surprising , but substantially inflating his publication record.....

Interestingly he did have some danio papers much later. Goodrich and Greene 1959 has been especially important to our own work on D. albolineatus.

Birds = dinosaurs = fish.
We seem to have an on-going selection experiment in this area. Should know more in a few years.

New model system. ASIP (a-y/a-t); MC1R (E-m/+); MFSD12 (i/+); TYRP1 (b-s/+); MITF (s-p/+); RALY (+/+). IYKYK.
Also a very good boy.

We think this is going to be a very useful system for studying the evolutionary origins of new cell types, important for understanding organismal complexity, diversification and behaviors. Thanks to our great collaborators and to NIGMS for supporting the work.

So what's all this mean? The upshot is that we find a lot of ways to make white cells, this being a very different mechanism from that of another population even in zebrafish
doi.org/10.1073/pnas...

Metabolomic analyses (eew, chemistry) confirmed differential accumulation of pale/white/colorless over yellow pigment in the transition of xanthophore-like (~X) cells to "xantholeucophores" (~XL).

This suggested that sepiapterin reductase might be changing yellow pteridine to pale or colorless pteridines and that other pteridine genes might be upregulated in these cells. Pathway enrichment analyses showed that was true, with these hits in the pteridine pathway (among others not shown):

Same target in white cloud minnow also gets rid of the white material.

And indeed when we knocked it out, we turned the white cells back to yellow.

We asked about other genes by RNA-seq and found a good candidate in sepiapterin reductase (spra/b), in the pteridine pigment pathway.

And their differentiation from these xanthophore-like cells requires gap junctional communication as well as the aquaglyceroporin and peroxiporin channel Aquaporin 3a, which we show is mutated in duchamp.

Here we focused on white cells, leucophores, that are present in zebrafish, with spots of carotenoids, and also leucophores in white cloud minnow. In zfish we used fate mapping to show the cells arise from xanthophore-like progenitors in the fin.

Just in time for the New Year we have a new preprint up that focuses on white cells, often used as ornaments in fish.
www.biorxiv.org/content/10.6...

So signaling at the molecular level allows for signaling at the organismal level, with lots of room for fine-tuning. Fun project with insights we wouldn't have gotten without the multi-level approach. Thanks as always to great collaborators and to NIGMS. Now we just need to start breeding peacocks.

Our take-home model is that graded variation in BMP signaling activity, combined with thresholds for cell-fate specification, sets up pattern in the fin (interpreted differently across species).

And even "closer to home" we found that BMP signaling was essential for patterning zebrafish fins.

What's more is that the pathway is conserved across species. When we looked at white cloud minnow, here too we had differential BMP activity between cell types and BMP-dependence of fate specification and pattern.

We then asked if there is standing genetic variation. There is and it maps to several regions but especially on chromosome 23, which is chock full of BMP pathways genes differentially expressed between these cells types.

So does this matter to the fish? We decided to use one of these mutants, along with a yellow mutant we made previously, to find out. In binary shoaling preference assays, the super-red BMP mutants were preferred over wild-type and the yellow-only fish.

And when we generated mutants in the BMP signaling pathway we got "super-red" fish, because of changes in both cell type specification and carotenoid contents.

BMP inhibition likewise shifted the numbers and distributions of these cells.

To understand how red vs yellow is determined we used a transcriptomic approach, which pointed to BMP pathway involvement. By immunostaining red erythrophores had much less BMP activity than yellow xanthophores.

We decided to look at pearl danio, Danio albolineatus, because reds, oranges and yellows are often important in signaling, and this species has red erythrophores and yellow xanthophores. These fish are very close to zebrafish, which doesn't have erythrophores.

But it is about signals. Animals communicate in all sorts of ways and some have elaborate and costly signals. Occasionally we know about allelic variation that contributes to variation in signaling traits. We almost never know how these signals are built developmentally.