Here are the highlights from the new issue of Development – the first one of the year. Happy reading…and Happy New Year!
Embryos rewired: the changing metabolome of early embryogenesis
During early mammalian embryogenesis, the developing embryo must adapt to changing metabolic demands and substrate availability. It has long been thought that a metabolic shift from glycolysis to OXPHOS takes place during this period and may be linked to the onset of choroallantoic branching, a major milestone in placental development that increases nutrient availability via the maternal circulation. But a simple shift from glycolysis to OXPHOS cannot explain how the array of macromolecules that are required to fuel cell proliferation are made, since OXPHOS produces mainly cellular energy and little else. Now, on p. 63, Yoshifumi Yamaguchi, Masayuki Miura and colleagues revisit this theory using state-of-the-art mass spectrometry techniques to survey the carbon flow of intracellular metabolites in the whole mouse embryo from embryonic day (E) 8.5 to E10.5, the period in which extensive choroallantoic branching occurs. The authors first establish the metabolic profile of the embryo during this period and show that, while metabolites indicative of OXPHOS do increase over this period, this is not accompanied by a decrease in glycolysis. Rather, the end product of glycolysis, lactate, also increases markedly from E8.5 to E10.5. The authors observe a decrease in the activity of phosphofructokinase-1 and go on to show how this results in the redirection of glucose into the pentose phosphate pathway, which is key for biomass production. This study provides insight into the dynamic metabolic profile of the developing embryo and sheds light on the long-standing question of whether and how a metabolic shift occurs during choroallantoic branching.
A new rule for spiral cleavage school
Spiral cleavage – the process by which cells of the early embryo divide and spiral around the pole-to-pole axis of the embryo – is the most common mode of animal development. Many hypotheses exist to explain how the precise spatial arrangement of cells is coordinated during this process, but to date there has been no systematic approach to verify which, if any, of these hypotheses are true. Now, on p. 54, Isaac Salazar-Ciudad and colleagues construct a computational framework in order to simulate early spiral cleavage behaviour. Using this model, they are able to constrain the behaviour of cells with existing hypotheses so as to determine which are important for the emergence of spiral cleavage and which are not. The authors find that none of the hypotheses proposed over time can produce the precise arrangement of cells observed during spiral cleavage, but that a small subset of them can do so if combined. Specifically, animal-vegetal polarization of cell division, Sachs’ rule in which cell division is oriented perpendicularly to the previous cell division, cortical rotation and adhesion are the main contributing variables to spiral cleavage. Finally, the authors show that their model can be used to generate a range of different embryo geometries corresponding to what is seen in seven different spiralian species. This elegant study highlights the power of computational approaches in understanding developmental processes, and brings insight into the specific parameters that govern spiral cleavage.
A supporting (cell) role for Wt1 in gonad development
The developing mammalian gonad comprises multiple different cell types, each with unique and important roles. Among these are the germ cells, which eventually become gametes and are crucial for generational inheritance, as well as supporting cells and steroidogenic cells, which support and nourish the gametes and provide important hormonal regulation, respectively. Despite the importance of supporting and steroidogenic cell types, the molecular mechanism that leads to their specification remains unclear. In this issue, on p. 44, Fei Gao and colleagues uncover a mechanism by which the expression of Wilms’ tumor 1 (Wt1) directs the lineage specification of supporting cells via the suppression of steroidogenic factor 1 (Sf1). Sf1 usually directs the specification of steroidogenic cells; however, the authors show that Wt1 binds directly to the promoter region of Sf1 in both sexes, supressing its expression. Deletion of Wt1 in the mouse undifferentiated genital ridge somatic cells before sex determination completely blocked the differentiation of the supporting Sertoli (in male) and granulosa (in female) cells, and resulted in the differentiation of steroidogenic cells instead. This study provides novel insight into somatic cell differentiation during gonadal development and provides a molecular mechanism for the specification of the supporting cells in both sexes.
The times they are a-changin’
The past 15 years have witnessed major evolutions in the field of developmental biology – in imaging technology, genome editing, development of new ‘model’ systems and many other areas. In his Editorial, Development’s Editor in Chief Olivier Pourquie highlights how Development has evolved with these changing times and discusses the journal’s plans for the future.
Towards a CRISPR view of early human development: applications, limitations and ethical concerns of genome editing in human embryos
The application of CRISPR-Cas technology to human cells has evolved in parallel with increasingly powerful methods of cell culture and analysis, and it is now possible to modify the genome of a human embryo in a highly efficient and specific way. In their Spotlight article, summarize the CRISPR-Cas genome editing system and discuss its potential applications and limitations in human pre-implantation embryos, and the ethical considerations thereof.
From stem cells to human development: a distinctly human perspective on early embryology, cellular differentiation and translational research
In late September 2016, over 100 scientists with common interests in human development, disease and regeneration gathered for The Company of Biologists’ second ‘From Stem Cells to Human Development’ meeting, which was held in historic Southbridge, USA. In their Meeting Review, highlight some of the exciting new findings that were presented, and discuss emerging themes and convergences in human development and disease that arose during these discussions.
Understanding development and stem cells using single cell-based analyses of gene expression
In recent years, genome-wide profiling approaches have begun to uncover the molecular programs that drive developmental processes. In their Review, Patrcik Cahan and colleagues discuss how single-cell RNA sequencing has provided key insights into mammalian developmental and stem cell biology, emphasizing the analytical approaches that are specific to studying gene expression in single cells.