Old and new: developmental biologists meet among the redwoods
The conference’s tagline, ‘Old and new: modern answers to enduring questions in development’, was introduced beautifully by the opening three keynotes.
Judith Kimble gave a fantastic career retrospective on her quest to understand how embryos get in and out of totipotent states. She described the 27 year search for Notch targets that maintained a naive stem cell fate, and how it lead them to two redundant low complexity proteins with no domains and no clear homologs in other species. This lack of conservation or functional domains dissuades many of us from working on such factors, but the importance of such proteins in development was a theme of the meeting, popping up in several talks.
Eric Wieschaus explained how genetically determined cell fates are translated into local cell behaviors, discussing how myosin tension is a regulator of morphogenetic sequences. He also nicely touched upon his scientific philosophy of reducing his work to the simplest model, seeing what it lacked, and then refining his model. Good lesson for trainees! [reductionist?]
Vilaiwan Fernandes, who has just started her own lab in UCL with a Wellcome Trust Sir Henry Dale Fellowship, won the SCDB Young Investigator Award. Her award lecture covered her time as a postdoc in Claude Desplan’s lab, where she worked on the establishment of retinotopy in the fly brain. She found that glia provide a key link between photoreceptors in the retina and target cells of the optic lobe. The differentiation of both types of cells needs to be tightly coordinated, and Vilaiwan found that glia are crucial to this process by forming a signalling relay, in part using insulin. Aidan got to interview Vil over a beer at a poster session – you can hear all about her research career and plans for the future in the associated interview.
The next two days provided repeated demonstrations of why developmental biology is such an exciting field at the moment, as new tools unlock fundamental questions that have kept the field busy for decades. There were so many amazing talks, and we will cover select ones to give readers a flavor of the meeting.
Dominique Bergmann introduced the problem of how cells and tissues establish polarity. Plants, which evolved multicellularity independently of animals, do things quite differently, not just in terms of the components involved but also in terms of how processes like symmetry breaking are achieved. She shared wonderful, long-term videos of asymmetric divisions in the plant stomatal lineage, and explored the reasons why can the establishment of polarity can take hours in plants compared minutes in something like a C. elegans embryo. This talk was another place in which small proteins of low complexity, no domains or conservation played a starring role.
Sally Horne-Badovinac asked how cells coordinate their migration with one another when moving collectively as a sheet. Follicle cells of the Drosophila ovary migrate around the growing egg chamber using basement membrane as a substrate, and this migration leads to the rotation of the egg chambers in a process thought to promote their elongation (it’s just such a bonkers way of sculpting a tissue, evolution really getting creative). Sally showed that the coordinated migration of follicle cells is regulated by the same molecules used in axon guidance, an example of how neurons and epithelia are closer to one another than we might usually think.
Shuonan He, a graduate student in Matt Gibson’s lab who also won the People’s Choice Award for his terrific poster, addressed the role of Hox genes in Cnidaria, which lack a true A-P axis and therefore provide a bit of a conundrum for those of us who think about Hox genes only in relation to A-P patterning. To tackle this problem, Shuonan utilised shRNAs knockdown and CRISPR/Cas9 knockouts to test Hox functional roles, and, with beautiful pictures of Nematostella cross sections, showed that Hox genes control tissue segmentation and tentacle patterning. It was a wonderful evo-devo story, hastened by the use of modern gene editing tools.
Taking a break from the multicellular, Laura Landweber took us somewhere truly strange – the astounding genome rearrangements that occur in the ciliate Oxytricha trifallax during its sexual reproduction. Oxytrichia has two genomes, one of which comprises over 16,000 chromosomes, most of which encodes a single gene; this ‘macronuclear’ genome has to be made anew from a micronuclear precursor during sexual reproduction, in a process of lncRNA-regulated genomic acrobatics that made many heads spin in the audience. It’s an incredibly powerful system to investigate genome fidelity across generations, and it was wonderful to hear about this in a development meeting.
Another major theme of the meeting was the power of single molecule approaches. Jeff Farrell and Sean Megason both presented their single cell RNA-seq (scRNA-seq) approaches to map zebrafish developmental trajectory. Dozens of distinct cell populations could be found by 12 hours of development. This work promises to answer major questions in developmental biology, such as how do cell states change over time and what paths can cells take through development?
Alejandro Sanchez-Alvarado identified the elusive planarian neoblast — the stem cell that allows for the amazing regenerative capacity of this animal — using scRNA-seq. Stunningly, a single neoblast could rescue viability and restore all cells in a lethally irradiated animals, which would otherwise dissolve into goop. Fun fact he shared: the strain of planarian they work on has lost sexual reproduction through a single translocation and now reproduce by anchoring their tail, crawling away until a fragment of their tail rips off, after which both halves generate entire new animals. Kristy Red-Horse used scRNA-seq to understand cell dynamics during coronary development, revealing that there is a gradual, overlapping transition of veins to arteries. Long Cai described sequential fluorescence in situ hybridization (seqFISH), which allowed single cell, single molecule detection of hundreds of transcription factor mRNAs or over 10,000 genomic loci by intron seqFISH.
There were also numerous talks using other powerful new techniques. Ari Pani explored Wnt signaling in C. elegans, providing evidence that a particular Wnt was using a signaling gradient, not a contact-based mechanism such as cytonemes. He used a clever MorphoTrap to disrupt the gradient without altering receptor or ligand levels and found Wnt diffusion was essential for neuroblast migration. Maria Barna used cutting edge mass spec to explore ribosome diversity, providing evidence for ribosomal proteins that associate only with a subset of ribosomes and allow translation of specific mRNAs
Like potato chips in sandwiches, the final keynote pairing of a talks on the morphogenetic Hox clock and evolution of forest mouse tail length was unexpectedly delicious. Denis Duboule gave an energetic, engaging broad overview of his work on Hox gene topologically associating domains. He also discussed the curious case of Hoxd13, which acts as a dominant negative to inhibit the other Hox proteins and seems to “mark the end of things, like digits”. Hopi Hoekstra’s keynote to close out the meeting started off exploring difference in forest mouse morphology, first observed by Osgood in 1909. Forest mice had longer tails due to both longer and more vertebrae, and these long tails were important for balance in lab tests. QTL mapping found three QTLs for length of longest vertebra, three for number of vertebra. And circling back beautifully to the first talk, these QTLs involved the Hox genes Duboule discussed in his talk. This session was a beautiful example of how the mechanisms we discover in the lab function in nature.
On the final night we had dinner outside and a final chance to discuss old questions and new techniques under the redwoods, those giants that miraculously, like all of us, started life as a single, tiny cell. The fog rolled in from the Pacific to envelop campus and left some of us lost in search of the bar, but we got there in the end (thanks to the student volunteers for supplying the drinks and acting as deeply knowledgeable beer sommeliers!).
The next Santa Cruz meeting is scheduled for 2020 – we would urge anyone keen on a smallish, diverse and relaxed development meeting in a stunning location to apply.
Did somebody say miraculously? 🙂