In this month's journal club we discussed a paper from Vatsala Thirumalai's lab (https://doi.org/10.1523/ENEURO.0493-20.2021). The paper was chosen by Kendra, who is interested in the zebrafish touch response circuit. Co-first authors Urvashi Jha and Igor Kondrychyn investigated the role of auts2a in zebrafish Mauthner cells and how it affects escape behavior. Using imaging, behavior paradigms, and electrophysiology, they show that auts2a mutants display highly variable success in their escape response, stemming from a higher threshold in Mauthner cells. We were particularly intrigued by the auts2a mutant data, where the variability seems to arise from two groups: those similar to wild types and those with highly delayed escape responses. What causes the differences between these groups? It would be interesting to tease apart the differences between the mutant phenotypes!
"Zebrafish Cdx4 regulates neural crest cell specification and migratory behaviors in the posterior body"
For our September journal club, we read the recently published paper by Dr. Manuel Rocha from his PhD work in the Prince lab, “Zebrafish Cdx4 regulates neural crest cell specification and migratory behaviors in the posterior body”. This paper includes beautiful images from our favorite model organism and introduces a new gene, cdx4, involved in neural crest (NC) cell specification and segmental migration in the zebrafish trunk. The analyses include an array of techniques from in situ hybridization chain reaction, to single-plane illumination microscopy and some complex bioinformatics! Together, their studies demonstrate that cdx4 not only establishes migratory behaviors of NC cells in the trunk but that it also regulates posterior expression of foxd3 during early development. Further, their work uses cdx mutants and chimeras created via cell transplantation to dive deeper into how cdx4 expression affects trunk NC cell dynamics. Really cool developmental work and we highly recommend checking it out for yourself!
“The epigenetic state of PRDM16-regulated enhancers in radial glia controls cortical neuron position”
For our August journal club we discussed a paper from 2018 from the lab of Dr. Corey Harwell, titled “The epigenetic state of PRDM16-regulated enhancers in radial glia controls cortical neuron position”. This well-rounded paper, which shows how a chromatin-modifying enzyme regulates a neurodevelopmental process, was a crash course for those of us in the lab who are novices in the field of epigenetics.
In the mammalian cerebral cortex, upper layer projection neurons develop in a process whereby radial glia (RG) give rise to intermediate progenitor (IP) cells that divide and then produce pairs of cortical neurons. Previous work showed that PRDM16, a chromatin-modifying enzyme, regulates neural stem cell maintenance and differentiation in the developing brain, and the Harwell group wanted to learn how this protein regulates gene expression in the developing cerebral cortex. Using beautiful immunofluorescent imaging and conditional knock-out (cKO) experiments, PRDM16 expression in RG is shown to promote production of IP cells and upper layer cortical neurons. RNA-seq and ChIP-seq experiments were performed and showed that PRDM16 regulates the transcriptional activation or silencing of genes important for the differentiation of RG into IP cells by epigenetic modification of enhancer regions. The strong activation of the E3 ubiquitin ligase Pdzrn3 in the cKO cortex suggests that it is normally silenced in RG by PRDM16 to promote upper layer cortical neuron migration. This is supported by the rescue of the upper layer cortical neuron defect by knocking down both Prdm16 and Pdzrn3. Finally, more beautiful imaging shows that the histone methyltransferase domain of PRDM16 is required for the silencing of Pdzrn3. Altogether, this paper does a nice job of showing how epigenetic regulation of gene transcription plays a role in setting up neuronal organization in the cortex. Thanks Harwell group for a great paper!
“Inflammation and matrix metalloproteinase 9 (Mmp-9) regulate photoreceptor regeneration in adult zebrafish”
For journal club this week, we read a paper from Dr. Nicholas Silva who published this work last year in Glia, titled “Inflammation and matrix metalloproteinase 9 (Mmp-9) regulate photoreceptor regeneration in adult zebrafish”. These findings came out of his PhD work in the Hitchcock lab at the University of Michigan.
This was a fun zebrafish glia paper with beautiful images and neat techniques (some of us were new to the zymogram!) that investigates how the inflammatory environment affects the ability of Müller glia to proliferate and differentiate into new rods and cones after photoreceptor injury. During this injury response, Müller glia highly express a matrix metalloproteinase, Mmp-9. It turns out that if the glia don’t express mmp9, they increase proliferation and make more photoreceptors. Overproduced rods persist over time, however, cones die. Cone survival can be rescued in mmp9 mutants by suppressing the immune response later in time with dexamethasone, suggesting that Mmp-9’s influence on the inflammatory ‘soup’ affects photoreceptor regeneration.
Of course there’s more twists and turns to the story, so we encourage you to check out the paper for yourself! We look forward to reading Nick’s future work as a postdoc in the Molofsky Lab and beyond.
"A muscle-epidermis-glia signaling axis sustains synaptic specificity during allometric growth in Caenorhabditiselegans”
Today in journal club, the lab discussed a recent study led by Daniel Colón- Ramos published in eLife, entitled “A muscle-epidermis-glia signaling axis sustains synaptic specificity during allometric growth in Caenorhabditis
Glia, genetic tools & confocal imaging in a model organism... All what we love, in one paper!!
As organisms grow to reach their adult size, organs and tissues have to scale up in size too. How do complex neural circuits and synapses that are established during embryogenesis maintain their precise position and
connectivity over such a dramatic change, is a fascinating question. Fan et al found that mig-17, a conserved ADAMTS metalloproteinase secreted from muscles, degrades basement membrane proteins and regulates glial
morphology and position in the worm brain. In turn, these glia that surround the nerve ring regulate synapse positions.
This study underscores the role of non-neuronal cells in maintaining synapse positions during allometric growth of the CNS and reminds us that glia are AWESOME!
"Specification of select hypothalamic circuits and innate behaviors by the embryonic patterning gene dbx1"
In the first of a meeting of a new journal club in the Kucenas lab, Maria Ali presented a paper entitled "Specification of select hypothalamic circuits and innate behaviors by the embryonic patterning gene dbx1" produced in a collaboration between the labs of Kevin Smith and Joshua Corbin and led by Katie Sokolowski. Our lab in particular discussed our appreciation for the paper to go from a gene of interest to investigating the gene's role in both neuronal and behavioral functions. The paper also highlighted the ability to identify a gene involved in regulating innate behaviors.