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In Development this week (Vol. 144, Issue 19)

Posted by , on 3 October 2017

Here are the highlights from the current issue of Development:

 

Making a move: EMT holds the key to planarian regeneration

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During development and wound healing, progenitor cells are required to migrate to different locations before they can differentiate into terminal tissue types. This cell migration often involves epithelial-to-mesenchymal transition (EMT), a process by which cells delaminate from an epithelium and become motile. On page 3440, Aziz Aboobaker and colleagues investigate how neoblasts, the adult stem cell population present in planarians, are able to migrate to sites of damage in order to regenerate tissue after irradiation. Using a shielded X-ray irradiation assay, they show that neoblasts require β-integrin and the activity of a matrix metalloproteinase to interact with the extracellular matrix and move through the tissue, just as in EMT. In addition, they show that migration requires EMT-associated transcription factor orthologs, such as snail-1snail-2 and zeb-1. Strikingly, the differentiation status of cells also affects their ability to migrate. Finally the authors report that, even in the absence of wounding, a notum-dependent signal from the brain, which normally lacks resident stem cells, draws in migrating neoblasts to maintain tissue homeostasis. Together, these results suggest that EMT-related mechanisms controlling cell migration are conserved among bilaterians and provide insights into how progenitor populations move to a site of wounding before regeneration begins.

 

How mouse oocytes give DNA damage the SAC

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Cells in embryos and adult tissues have mechanisms that allow them to identify and respond to DNA damage, thereby ensuring that deleterious mutations cannot arise and persist in individuals. On page 3475, Keith Jones and colleagues investigate the mechanism by which mouse oocytes arrest upon DNA damage. This response involves activation of the spindle assembly checkpoint (SAC), which normally prevents the onset of anaphase until all chromosomes are correctly attached to the spindle. In this study, the authors find that, within minutes of DNA damage, SAC-associated proteins are not recruited to the sites of damage along chromosome arms, but instead become concentrated at the chromosome kinetochores, which act as a platform to generate the SAC signal. SAC activation is dependent on the activity of aurora kinase and MPS1 kinase but, interestingly, does not rely on PI3K-related kinases important for the DNA damage response in other systems. Furthermore, the authors show that the arrest response is unique to oocytes in meiosis I and does not occur in oocytes undertaking meiosis II. These results uncover a new mechanism by which DNA damage is dealt with in oocytes and provide clues into how the formation of genetically abnormal embryos is prevented.

 

Imp and Syp call time on Drosophila neuroblasts

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Drosophila neurons are born from progenitors, known as neuroblasts, in a temporally controlled manner. Given that the timing of birth affects the type of neuron that is generated, this process must be tightly regulated over time so that a diverse array of neuronal progeny is produced. The RNA-binding proteins IGF-II mRNA-binding protein (Imp) and 15 Syncrip/hnRNPQ (Syp) are known to exhibit temporally graded expression patterns in neuroblasts, and have thus been shown to regulate the process of neuronal fate specification. Now, on page 3454, Tzumin Lee and colleagues uncover a role for Imp and Syp in neuroblast decommissioning, as well as in neuron differentiation. ‘Decommissioning’ is the process by which neuroblasts shrink and exit the self-renewing progenitor state before forming terminally differentiated neurons. The authors find that Imp and Syp are crucial for this two-stage ‘decommissioning’ process. Imp regulates shrinkage of the neuroblast so that this event does not occur prematurely, while Syp acts subsequently to promote the accumulation of Prospero in the nucleus, leading to cell-cycle exit. Together, these results provide a mechanism by which neuroblast decommissioning occurs in the Drosophila brain and enhance our understanding of how neural stem cells are controlled during development.

 

PLUS:

 

An interview with Jayaraj Rajagopal

Embedded ImageJayaraj (Jay) Rajagopal is a Principal Investigator at the Center for Regenerative Medicine at Massachusetts General Hospital and an Associate Professor of Medicine at Harvard Medical School. His lab works on the development and regeneration of the lung, using stem cell and animal models to develop novel insights that hopefully will provide inspiration for therapies to help treat human lung disease. In 2017, he was awarded the Dr Susan Lim Award for Outstanding Young Investigator at the International Society for Stem Cell Research (ISSCR) meeting in Boston (MA,USA), where we met him to talk about how a fish tank started a life-long fascination with the lung, the transition to running his own lab, and his optimism for the future of both basic stem cell research and its clinical translation. Read the Spotlight article on p. 3389.

 

On the evolution of bilaterality

Fig. 1.Bilaterality – the possession of two orthogonal body axes – is the name-giving trait of all bilaterian animals. These body axes are established during early embryogenesis and serve as a three-dimensional coordinate system that provides crucial spatial cues for developing cells, tissues, organs and appendages. How bilaterality evolved and whether it evolved once or several times independently is a fundamental issue in evolutionary developmental biology. Recent findings from non-bilaterian animals, in particular from Cnidaria, the sister group to Bilateria, have shed new light into the evolutionary origin of bilaterality. In their Hypothesis article, Grigory Genikhovich and Ulrich Technau compare the molecular control of body axes in radially and bilaterally symmetric cnidarians and bilaterians, identify the minimal set of traits common for Bilateria, and evaluate whether bilaterality arose once or more than once during evolution.

 

The PAR proteins: from molecular circuits to dynamic self-stabilizing cell polarity

Fig. 1.PAR proteins constitute a highly conserved network of scaffolding proteins, adaptors and enzymes that form and stabilize cortical asymmetries in response to diverse inputs. They function throughout development and across the metazoa to regulate cell polarity. In recent years, traditional approaches to identifying and characterizing molecular players and interactions in the PAR network have begun to merge with biophysical, theoretical and computational efforts to understand the network as a pattern-forming biochemical circuit. In their Review article, Charles Lang and Edwin Munro summarize recent progress in the field, focusing on recent studies that have characterized the core molecular circuitry, circuit design and spatiotemporal dynamics.

 

 

Can injured adult CNS axons regenerate by recapitulating development?

In the adult mammalian central nervous system (CNS), neurons typically fail to regenerate their axons after injury. During development, by contrast, neurons extend axons effectively. A variety of intracellular mechanisms mediate this difference, including changes in gene expression, the ability to form a growth cone, differences in mitochondrial function/axonal transport and the efficacy of synaptic transmission. In turn, these intracellular processes are linked to extracellular differences between the developing and adult CNS. During development, the extracellular environment directs axon growth and circuit formation. In adulthood, by contrast, extracellular factors, such as myelin and the extracellular matrix, restrict axon growth. In their Review article, Brett Hilton and Frank Bradke, we discuss whether the reactivation of developmental processes can elicit axon regeneration in the injured CNS.

 

 

 

 

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