Joana Estaves De Lima, Boston, 25-30 July 2019

78th Annual Meeting of the Developmental Biology Society

→ 500 € Prize

Postdoc with Frédéric Relaix, INSERM U955, Créteil

The 78th Annual Meeting of the Society for Developmental Biology (SBD) was also the moment to celebrate the 80th anniversary of the Society. The meeting was held in four days that included plenary and concurrent sessions and had 648 scientific communications, including oral presentations and posters. I will further highlight a few talks that described the progress of new techniques and defined new mechanisms in developmental biology.

On the genome editing session, I would like to mention the talk by Feng Zhang, Massachusetts Institute of Technology, which has significantly contributed to the advance of the Crispr/Cas9 technology. In his talk, Zhang showed us a new technique by which Crispr-associated transposases can prime targeted insertions of DNA into the genome, a procedure that remains a challenge in the field. Although the transposase catalyzes RNA-guided DNA transposition by inserting small fragments of DNA (around 60 base pairs) downstream of the protospacer, this seems to be a promising technique to overcome the difficulty of targeting DNA insertions.

From the evolution session, the talk by Denis Duboule, École Polytechnique Fédérale de Lausanne, on the three-dimensional organization of the Hoxb cluster stood out for the usage of gastruloids as a complementary system to the mouse model to study changes in expression of the Hoxb cluster. In Duboule’s laboratory, researchers used gastruloids to describe the role of Hoxb13, that is physically distant from the remaining Hoxb genes, in the establishment of the anterior to posterior axis. Hoxb13 was shown to play a role as terminator of the tail development based on the fact that when Hoxb13 is expressed ectopically, due to the excision of the regulatory domains present between Hoxb13 and the remaining Hoxb genes, the tail size was smaller.

A highlight of the conference was the talk by Sir John Gurdon, Gurdon Institute, Nobel prize for physiology or medicine for his studies on nuclear transfer, reprogramming and epigenetic memory. Gurdon studies the mechanisms that are behind the stability of cell differentiation given the observation that gene expression is increasingly stable as cells differentiate. In Gurdon’s laboratory, researchers use luciferase assays combined with DNA competitive assays to assess function and to analyze the time of residence of transcription factors (TFs) on DNA. It was interesting to appreciate that a plasmid transfected into a cell at a higher concentration can recruit the TF from a first plasmid, previously transfected, showing that the TF displays a short residence on DNA. Although, it is important to remember that TFs bind chromatin within a genomic context and not only to DNA. Therefore, the researchers engineered ectopic binding sites for specific TFs within the genome of the cells. In this case, the transfection of a plasmid into these cells cannot displace the TF from the genomic engineered binding sites, showing a long-term residence of the TF and a consequently stable gene expression. Therefore, the epigenetic context of the chromatin is of major importance to understand the means of action of TFs. Allon Klein, Harvard University, gave a talk on the tracing of clonal dynamics on transcriptional landscapes, depicting possible problems with the general analysis of pseudotime used in single-cell RNA-sequencing (scRNA-seq). Klein asked the question whether scRNA-seq is predictive of fate progression of the embryonic cell lineages from pluripotency to differentiation and if pseudotime actually reflects real time. For that, the researchers performed scRNA-seq in zebrafish embryos at different timepoints. The results showed that the differentiating cells of the zebrafish embryo do not always follow tree-like hierarchies. Instead, the researchers observed both cases: clonally distant cells ending up in convergence and clonally related cells diverging into distinct states upon bioinformatics analysis. The convergence of different cell states could be explained by the differentiation of well-separated spatial domains of the embryo into the same cell type, while divergence could involve mechanisms such as asymmetric cell division.

In the regeneration session, Jessica Whited, Harvard University, showed us how the regenerative capacity of axolotl’s limbs declines when amputated several times at the same plane. Whited showed that after five subsequent amputations, the blastema, transitory structure required for correct regeneration, upregulates fibrosis-associated genes. After performing a transcriptomic analysis, Whited laboratory identified Eya2 as being upregulated upon a single injury but absent after five amputations. They identified a mechanism by which Eya2 modulates the phosphorylation state of H2AX and the cell response to DNA damage. This signaling cascade is required to inhibit cell death by apoptosis and maintaining the blastema cells, leading to a proper regeneration.

From the plenary session of patterning, I would like to describe the more recent studies from the laboratory of Marianne Bronner, California Institute of Technology. Bronner’s laboratory research is based on the study of neural crest cells. In this conference, Bronner showed us how cranial neural crest-specific genetic circuit was built during evolution. In this study, the researchers used chicken and lamprey embryos as models to characterize the transcriptomes of the cranial neural crest cells in an evo-devo context. Key genes expressed in the chicken cranial neural crest circuit are not expressed in lamprey cranial neural crest cells. Although, interestingly, lamprey cranial neural crest cells transcriptome is more similar to the trunk neural crest of chicken embryos, indicating that the expression of genes from the cranial neural crest circuit of tetrapods were progressively added during evolution.

As a final note on the SDB conference I would like to mention the two major awards of the society: the Lifetime Achievement award that was granted to Christiane Nüsslein-Volhard, Max Planck Institute, Nobel prize for physiology or medicine, for her discoveries on the genetics behind the patterning of developing embryos; and the Edwin G. Conklin Medal awarded to Eric Olson, University of Texas Southwestern, for his career achievements that contributed profoundly to the understanding of the signaling pathways regulating skeletal muscle development and regeneration.