In Development this week (Vol. 144, Issue 18)

Here are the highlights from the current issue of Development:

Separating nematode species by spermatogenesis

During spermatogenesis, unnecessary organelles and cytoplasmic components are shed from developing sperm in order to streamline them for optimal motility. These components are partitioned into structures known as ‘residual bodies’, which subsequently separate from the sperm and are lost. In the nematode worm C. elegans, this partitioning occurs immediately after the meiotic divisions, thus accelerating the process of sperm production. On p. 3253, Diane Shakes and colleagues exploit the interspecies diversity in spermatogenesis among nematodes to reveal how cellular components become partitioned. Focussing on the role of microtubules and actin, they characterise the process in C. elegans and in another nematode species, Rhabditis sp. SB347, and find important mechanistic variations between the two. In Rhabditis, which produces small spermatocytes, two rather than four sperm are generated during meiosis; the rest of the genetic material is partitioned into residual bodies. Interestingly, this mirrors oocyte production and resulting polar-body formation in females. These results provide insight into both the conserved and divergent mechanisms that underpin partitioning during spermatogenesis, and reveal how these segregation mechanisms can be modulated to achieve differences between species.

Sending signals through SMADs: how blood flow shapes arteries

During organogenesis, mechanical forces can induce transcriptional and cytoskeletal changes in cells that help shape tissues as they develop. However, the mechanisms allowing cells to sense and respond to these mechanical signals are poorly understood. In the cardiovascular system, endothelial cells, which line the arteries, are able to change their shape in response to high or low blood flow through an artery, resulting in a change to the vessel’s diameter. On p. 3241, Kristy Red-Horse and colleagues investigate how mechanical signals are transduced by endothelial cells to regulate the size of arteries, and show that SMAD4 signalling mediates this response. When SMAD4 is deleted in mice, coronary artery size is increased, subsequent to the onset of blood flow. They also show that in human coronary artery endothelial cells cultured in vitro, knockdown of SMAD4 leads to defects in flow-guided cell elongation and migration. Additionally, they find that these cells undergo increased proliferation when exposed to shear stress. Their data directly link BMP/SMAD signalling to endothelial changes in response to mechanical force. These results increase our understanding of how forces can regulate tissue development during embryogenesis, and might be important in developing treatments for human vascular pathologies.

Opening up: new insights into chromatin decondensation

During heat shock, cells respond to temperature stress by opening their chromatin, allowing the transcription of genes that enable them to cope with the sudden change in the environment. How chromatin becomes decondensed to permit active transcription during this process is not clear. Recently, a model based on experiments in Drosophila has been proposed, whereby histone H2Av is deposited and subsequently phosphorylated by JIL-1 kinase, followed by recruitment of poly(ADP-ribose) polymerase 1 (PARP-1). PolyADP-ribosylation of chromatin then takes place, which loosens its structure. This permits phosphorylation of serine 10 in the tail of histone H3 (H3S10p), again by JIL-1 kinase, which is required for the function of the transcriptional machinery. On p. 3232, Kristen Johansen and colleagues test this model using null mutants and find that H2Av phosphorylation and chromatin opening can occur in the absence of JIL-1 kinase, and that H3S10p still occurs in a PARP-1 knockdown mutant. In light of these findings, the proposed model breaks down. Instead, the authors find that PARP-1 can be recruited by H3S10p independently of H2Av, providing insight into an alternative mechanism for opening up of chromatin structure to permit active transcription in Drosophila.

Histone demethylase functions in fertility

The acquisition and removal of epigenetic marks can help modulate gene expression during development by altering chromatin structure. Di- or tri-methylation of histone H3 on lysines 9 and 36 (H3K9/36) is associated with gene repression and silencing, since these marks induce a closed chromatin state. Kdm4a is an enzyme that demethylates H3K9/36, and functions to prevent the build-up of methyl groups at these sites in order to maintain active transcription. On p. 3264, Kristian Helin and colleagues now reveal a role for Kdm4a in female fertility. They show that this histone demethylase is expressed in all tissues of the female reproductive system, including the oocyte. While mice lacking the enzyme are able to ovulate and fertilise embryos normally, pregnancies fail because the embryos do not implant in most cases. Although the morphology of the reproductive tract is not altered in these animals, gene expression analysis shows that genes important for uterine receptivity are downregulated. Furthermore, maternal Kdm4a is also required in the oocyte to generate viable embryos, with knockout embryos arresting within the first few days after fertilisation. These results provide insight into how chromatin regulation through epigenetic factors can impact on physiological processes, including fertility.

PLUS…

An interview with George Daley

George Daley is Dean of the Faculty of Medicine, Professor of Biological Chemistry and Molecular Pharmacology, and Caroline Shields Walker Professor of Medicine at Harvard Medical School. A former Howard Hughes Medical Institute Investigator and President of the International Society for Stem Cell Research (ISSCR) from 2007-2008, his lab works on the biology and clinical application of stem cells, with a particular focus on hematopoiesis. He was awarded the Public Service Award at the ISSCR 2017 meeting in Boston, where we caught up with him to discuss his move from the lab to the clinic and back again, his quest to derive human hematopoietic stem cells in vitro, and his advocacy for science in uncertain political times. Read the Spotlight article.

Metabolism in time and space – exploring the frontier of developmental biology

In May 2017, a diverse group of scientists assembled at the EMBO/EMBL Symposium ‘Metabolism in Time and Space’ to discuss how metabolism influences cellular and developmental processes. The speakers not only described how metabolic flux adapts to the energetic needs of a developing organism, but also emphasized that metabolism can directly regulate developmental progression. Overall, this interdisciplinary meeting provided a valuable forum to explore the interface between developmental biology and metabolism. Read the Meeting Review by Alena Krejci and Jason Tennessen.

The enigma of embryonic diapause

Embryonic diapause – a period of embryonic suspension at the blastocyst stage – is a fascinating phenomenon that occurs in over 130 species of mammals, ranging from bears and badgers to mice and marsupials. It might even occur in humans. During diapause, there is minimal cell division and greatly reduced metabolism, and development is put on hold. Yet there are no ill effects for the pregnancy when it eventually continues. Multiple factors can induce diapause, including seasonal supplies of food, temperature, photoperiod and lactation. The successful reactivation and continuation of pregnancy then requires a viable embryo, a receptive uterus and effective molecular communication between the two. In their Primer article, Marilyn Renfree and Jane Fenelon provide an overview of the process of diapause, focusing on recent molecular data.

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