Neural circuit building

During development, sensory neurons form neural circuits with motoneurons. Although the anatomical details of these circuits are well described, less is known about the molecular mechanisms underlying their formation. To investigate the involvement of motoneurons in sensory neuron development, Hirohide Takebayashi and colleagues analyse sensory neuron phenotypes in the dorsal root ganglia (DRG) of Olig2 knockout mouse embryos, which lack motoneurons (see p. 1125). These embryos, they report, also have reduced numbers of sensory neurons but increased numbers of apoptotic cells in the DRG. In addition, the axonal projections of the sensory neurons in these embryos are abnormal. Because neurotrophin 3 (Ntf3) and its receptors are strongly expressed in motoneurons and sensory neurons, respectively, the researchers also investigate whether Ntf3 is one of the motoneuron-derived factors that regulate sensory neuron development. Notably, the sensory neuron phenotypes in Ntf3 conditional knockout embryos resemble those observed in Olig2 knockout embryos. Thus, the researchers propose, motoneuron-derived Ntf3 is a pre-target neurotrophin that is essential for survival and axonal projection of sensory neurons.

SIK3 bones up on chondrocyte hypertrophy

Most vertebrate bones develop through endochondral ossification. During this process, proliferating chondrocytes form a cartilage scaffold, differentiate into hypertrophic chondrocytes and die. The cartilage scaffold is then degraded and replaced by bone. Chondrocyte hypertrophy is, therefore, crucial for endochondral ossification. On p. 1153, Noriyuki Tsumaki and colleagues identify salt-inducible kinase 3 (SIK3) as an essential factor for chondrocyte hypertrophy in mice. SIK3-deficient mice, the researchers report, exhibit dwarfism, bone malformation and accumulation of chondrocytes in various bones. These phenotypes, they suggest, are due to impaired chondrocyte hypertrophy. Consistent with this suggestion, SIK3 is expressed in prehypertrophic and hypertrophic chondrocytes in the embryonic bones and postnatal growth plates of wild-type mice. Other experiments show that SIK3 anchors histone deacetylase 4 (HDAC4) in the cytoplasm, thereby releasing MEF2C, a transcription factor that facilitates chondrocyte hypertrophy, from suppression by HDAC4 in the nucleus. These results suggest that the regulation of HDAC4 by SIK3 is important for the progression of chondrocyte hypertrophy during skeletal development.

PRMT5 and stem cell function

Stem cells are essential for growth, development, gamete production and tissue homeostasis but what regulates their maintenance and function in vivo? On p. 1083, Phillip Newmark and colleagues report that the conserved protein arginine methyltransferase PRMT5 promotes stem cell function in planarian flatworms. These organisms contain a population of adult stem cells called neoblasts that can regenerate all the worm’s tissues. Neoblasts characteristically contain chromatoid bodies, large cytoplasmic ribonucleoprotein (RNP) granules similar to structures that are present in the germline of many organisms. The researchers show that, like germline RNP granules, chromatoid bodies contain proteins bearing symmetrical dimethylarginine (sDMA) modifications, probably including the PIWI family member SMEDWI-3. PRMT5 is responsible for sDMA modification of these proteins, they report, and PRMT5 depletion results in fewer chromatoid bodies, fewer neoblasts, and defects in regeneration, growth and homeostasis. Together, these results identify new chromatoid body components that are involved in neoblast function and add to the evidence that suggests that sDMA modification of proteins stabilises RNP granules.

BR(in)G1 on male meiosis

Mammalian germ cell development and gametogenesis involve several genome-wide changes in epigenetic modifications and chromatin structure. Here (p. 1133), Terry Magnuson and co-workers explore the role of the mammalian SWI/SNF chromatin-remodelling complex during spermatogenesis in mice. The researchers report that levels of the SWI/SNF catalytic subunit brahma-related gene 1 (BRG1) peak during the early stages of meiosis. Consistent with this expression pattern, germline ablation of Brg1 produces germ cells that arrest during prophase 1, the stage of meiosis during which the induction and repair of DNA double-strand breaks generates recombination between homologous chromosomes. In line with the timing of their meiotic arrest, BRG1-depleted spermatocytes accumulate unrepaired DNA and fail to complete synapsis. They also exhibit global alterations to histone modifications and chromatin structure, including alterations that are associated with DNA damage and heterochromatin. The researchers propose, therefore, that BRG1 has an essential role in spermatogenesis and that BRG1-containing complexes function in the programmed recombination and repair events that occur during meiosis.

Binary route to (non)-neural competence

During gastrulation, neural crest and cranial placodes originate at the neural plate border and from an adjacent territory, respectively. But do these ectodermal tissues arise from a common precursor or from neural and non-neural ectoderm (the binary competence model)? On p. 1175, Gerhard Schlosser and colleagues use tissue grafting in Xenopus embryos to tackle this controversy. They show that, at neural plate stages, competence for induction of neural plate, border and crest markers is restricted to neural ectoderm, whereas competence for induction of panplacodal markers is confined to non-neural ectoderm. The homeobox protein Dlx3 and the transcription factor GATA2 are both required cell-autonomously for panplacodal and epidermal marker expression in non-neural ectoderm, they report. Moreover, the ectopic expression of Dlx3 (but not GATA2) in the neural plate is sufficient to induce non-neural markers, whereas the overexpression of Dlx3 or GATA2 suppresses neural plate, border and crest markers in the neural plate. Together, these results support the binary competence model and implicate Dlx3 in the regulation of non-neural competence.

Morphogen-based simulation of fin development

One of the greatest challenges in developmental biology is to understand how shape and size are controlled during development. Interactions between growth and pattern formation mechanisms are key drivers of morphogenesis but are difficult to study experimentally because of the highly dynamic nature of development in space and time. Here (p. 1188), Anne-Gaëlle Rolland-Lagan and co-workers use simulation modelling to explore how mobile signals, such as morphogens, might coordinate growth and patterning during zebrafish caudal fin development and regeneration. The zebrafish fin comprises 16 to 18 bony rays, each of which contains multiple joints along its proximodistal axis that give rise to segments. The researchers propose a model in which the interaction of three postulated morphogens can account for the available experimental data on fin growth and joint patterning and for the regeneration of a properly shaped fin following amputation. This simple, plausible model provides a theoretical framework that could guide future searches for the molecular regulators of fin growth and regeneration.

Plus…

CTCF: insights into insulator function during development

The nuclear protein CTCF when bound to insulator sequences can prevent undesirable crosstalk between genomic regions and can shield genes from enhancer function. Here, Rainer Renkawitz and colleagues discuss the mechanisms underlying developmentally regulated CTCFdependent transcription. See the Primer on p. 1045

The hypoblast (visceral endoderm): an evo-devo perspective

Claudio Stern and Karen Downs discuss the function and evolution of the chick hypoblast and the visceral endoderm in mouse, highlighting the common roles played by these tissues. See the Review on p. 1059

ROCKed to the heart

Noonan syndrome – a common cause of congenital heart disease – is often associated with missense mutations in the protein phosphatase SHP-2. Interestingly, some types of leukaemia are associated with another subset of SHP-2 missense mutations. Here (p. 948), Frank Conlon and colleagues introduce SHP-2 that contains Noonan-associated mutations or juvenile myelomonocytic leukaemia (JMML)-associated mutations into Xenopus embryos to investigate how SHP-2 regulates heart development. Embryos that express SHP-2 containing Noonan-associated mutations have morphologically abnormal hearts, they report, whereas embryos that express SHP-2 containing JMML-associated mutations have normal hearts. The cardiac abnormalities caused by the Noonan-associated mutations are coupled with a delay or arrest in the cardiac cell cycle and with defective incorporation of cardiomyocyte precursors into the developing heart. Notably, these defects, which are caused by disruptions in the polarity of cardiac actin fibres and in F-actin deposition, can be rescued by inhibition of the Rho-associated, coiled-coil-containing protein kinase 1 (ROCK), which indicates that SHP-2 acts via ROCK to regulate the cardiac actin cytoskeleton during heart development.

Breaking symmetry during lateral root formation

Lateral root (LR) formation, which is essential for the construction of plant root systems, is initiated by coordinated asymmetric cell divisions (ACDs) of LR founder cells in existing roots. In Arabidopsis, LR formation is regulated by auxin signalling through the auxin response factors ARF7 and ARF19, which transcriptionally activate the plant-specific transcriptional regulator LBD16/ASL18 and other LBD/ASL genes. Hidehiro Fukaki and colleagues now provide new insights into the biological role of LBD/ASL genes in LR formation (see p. 883). They show that LBD16/ASL18 is expressed in Arabidopsis LR founder cells prior to ACD and that the spatiotemporal expression of LBD16/ASL18 during LR initiation is dependent on a specific auxin signalling module. Moreover, inhibition of LBD16/ASL18 and related LBD/ASL proteins in LR founder cells blocks nuclear migration, ACD and LR initiation. These results indicate that the localised activity of LBD16/ASL18 and related LBD/ASL proteins establishes the asymmetry of LR founder cells that is required for LR initiation, a key step in the construction of the plant root system.

Untangling the Hairy segmentation clock

During somitogenesis, an oscillating gene network generates a segmental pattern in the presomitic mesoderm. In zebrafish, this segmentation clock centres on cycles of transcription and self-repression of numerous hairy-enhancer of split related (her) genes, which encode proteins that dimerise, bind DNA and repress transcription. On p. 940, Scott Holley and co-workers systematically examine the physical interactions between Her proteins and test the ability of various Her protein dimers to bind to cis regulatory sequences. Dimerisation of Her proteins is specific, they report, with Hes6 serving as the hub of the network. Not all dimers bind to DNA, they note, but those that do so have distinct preferences for different cis regulatory sequences. Finally, Her7 disproportionately influences the availability of Hes6 for heterodimerisation with other Her proteins. The researchers propose, therefore, that Her7 has two functions within the zebrafish segmentation clock – direct repression of transcription through formation of a DNA-binding heterodimer with Hes6 and modulation of the network topology via sequestration of the network hub.

Diet and stem cells TORtuously linked

Nutritional status must be coupled to stem/progenitor cell proliferation and differentiation to ensure the proper growth and homeostasis of tissues, but how does diet regulate stem cell behaviour? On p. 859, E. Jane Albert Hubbard and colleagues show that rsks-1 [the homologue of mammalian p70 ribosomal S6 kinase (S6K), a target of the serine/threonine kinase TOR, which regulates cell growth and proliferation in response to nutritional cues] links cell fate, cell cycle and nutrient response in C. elegans germline stem/progenitor cells. They show that rsks-1 is required germline-autonomously to establish the proper number of germline progenitors, a role that requires a conserved TOR phosphorylation site in RSKS-1. Their analysis also reveals genetic interactions between rsks-1 and Notch, which suggest a prominent role for rsks-1 in cell fate control. Furthermore, dietary restriction causes germline defects similar to those observed in rsks-1 mutants and loss of rsks-1 renders the germline largely insensitive to dietary restriction. The researchers propose, therefore, that TOR-S6K signalling is a key nutrient-responsive regulator of germline progenitors.

Apical ECM and epithelial junction integrity

Polarised epithelial cells form many of the body’s surfaces, including the outer epidermis and the lining of several internal tubular organs. The apical surfaces of these epithelial sheets secrete a specialised extracellular matrix (ECM) that is generally viewed as a passive protective layer against pathogens, but does apical ECM have any other roles? According to Meera Sundaram and colleagues, the apical ECM in C. elegans might help to maintain epithelial junction integrity and, consequently, epithelial tissue integrity (see p. 979). The researchers report that the extracellular leucine-rich repeat only (eLRRon) proteins LET-4 and EGG-6 are expressed on the apical surfaces of epidermal cells and some tubular epithelia, including those of the worm’s excretory system. Mutants lacking one or more of these proteins, they report, have multiple defects in apical ECM organisation and, although epithelial junctions initially form correctly in these mutants, they subsequently rupture. Together, these results suggest that eLRRon-dependent apical ECM organisation might modulate epithelial junction dynamics and integrity.

Bimodal control of HoxD gene transcription

Correct innervation of peripheral muscles by spinal cord motoneurons is required to coordinate body movements in vertebrates. Hox proteins play an important functional role in achieving this innervation by specifying neuronal fates along the anteroposterior axis of the developing spinal cord. However, the mechanisms that generate Hox gene expression patterns are poorly understood. Here (p. 929), Denis Duboule and colleagues use tiling array-based transcriptome analyses and targeted deletions in vivo to investigate the control of HoxD gene transcription in the developing mouse spinal cord. They report that there are two distinct blocks of HoxD transcription that are regulated independently and that define two general expression territories. These territories, they show, are associated with the future nerve plexii at the brachial and lumbar levels. Given these and other results, the researchers propose that the establishment of spatial collinear HoxD domains in the developing mouse spinal cord involves the bimodal control of HoxD gene transcription by two independent ‘enhancer mini-hubs’.

Plus…

Human pre-implantation embryo development

Retinoic acid signalling during development

Retinoic acid is a vitamin A-derived signaling molecule that acts as ligand for nuclear receptors, converting them from transcriptional repressors to activators. Here, Muriel Rhinn and Pascal Dolle review the main functions of retinoic acid during embryogenesis. See the Primer article on p. 843

Neuronal cell fate: windows of opportunity

It is becoming increasingly evident that both vertebrate and invertebrate neural progenitor cells exhibit programmed temporal changes in their competence to generate specific neuronal cell types, but how is this competency controlled? Two articles in this issue address this question by studying Drosophila neuroblast lineage progression.

On p. 657, Michael Cleary and co-workers investigate the role of Polycomb repressor complexes (PRCs) in regulating neuroblast competence. In the Drosophila neuroblast 7-1 (NB7-1) lineage, the transcription factor Kruppel (Kr) specifies the third-born U3 motoneuron, but competence to generate U3 cells is limited to early divisions and is gradually lost when the neuroblasts transition to making interneurons. The researchers show that PRC loss of function extends the ability of Kr to induce U3 fate, whereas PRC gain of function causes precocious loss of competence to make motoneurons. The analysis of other neuroblast lineages that undergo a motoneuron-to-interneuron production transition demonstrates that PRCs also act to restrict motoneuron competence in these lineages. The researchers thus propose a model in which PRCs act to set up motoneuron-specific windows of competence in various neuroblasts that transition from motoneuron-to-interneuron production.

On p. 678, Stefan Thor and colleagues focus on the Drosophila embryonic neuroblast NB5-6T lineage to investigate how cell proliferation and cell fate specification are integrated during development. NB5-6T neuroblasts give rise to a lineage of 20 cells, including a differentiated set of neurons that are born at the very end of the lineage and that express Apterous: the Ap neurons. The authors identify two independent factors, Prospero and Notch, that act in concert to control the proliferation of NB5-6T daughter cells as the lineage progresses temporally; Prospero controls daughter cell proliferation in the early lineage and Notch activity then limits daughter cell proliferation in the late lineage, when Ap neurons are generated directly from neuroblasts, resulting in a programmed differentiation switch. Thus, the authors conclude, the control of neuronal daughter cell proliferation is integrated with temporal progression to ensure that the correct numbers of each unique cell type are generated.

Bypassing auxin signalling

Plant development is regulated by a number of mobile factors. The Arabidopsis BYPASS1 (BPS1) gene was previously shown to control shoot and root development by preventing formation of a mobile compound, but how this compound functions and whether it modulates other signalling pathways is unclear. Now, Leslie Sieburth and colleagues show that Arabidopsis BPS1, as well as two related genes, BPS2 and BPS3, control the production of a mobile factor, the bps signal, which regulates patterning and growth in parallel with auxin signalling (p. 805). By analysing single, double and triple mutants, the researchers show that all three BPS genes control bps signal synthesis. Importantly, bps triple mutants display severe embryogenesis defects, including disruptions to vascular, root and shoot stem cell populations. Finally, bps triple mutants exhibit normal auxin-induced gene expression and localisation of the PIN1 auxin transporter, suggesting that the bps signal functions in an auxin-independent manner. Although the nature of the bps signal remains unknown, these studies identify a novel pathway that regulates multiple stages of plant patterning and growth.

ABC of germline development

Plasma membrane ABC transporters serve dual functions in the cell: they export toxins to protect against damage and morphogens to mediate communication. It is thought that the activity of ABC transporters in embryos and stem cells should be high, so that mutagens are efficiently removed. Here, Joseph Campanale and Amro Hamdoun (p. 783) report the surprising finding that ABC transporter activity is reduced in germline precursors, the small micromeres, of the sea urchin embryo. This reduction in efflux pump activity can likely be ascribed to an increase in the rate of endocytosis specifically in the micromeres. What are the functional consequences of manipulating ABC transporter activity? The authors take a first step towards understanding this, showing that ABC transporter inhibition disrupts migration of the small micromeres at later stages of embryogenesis. While there is still much to be understood about the regulation and role of these plasma membrane pumps, this study provides evidence for the developmental importance of controlling their surface expression and activity.

Glutamate keeps hair follicles in touch

The hairs of our skin are mechanoreceptive: displacement of the hair is detected via sensory afferents in the hair follicle piloneural collar. In this complex structure, neurons, Schwann cells and keratinocytes are closely apposed, and interactions between these three cell types may influence differentiation and function of the piloneural collar. Here, David Owens and colleagues demonstrate that glutamate, which is known to mediate communication between neurons and Schwann cells in the central nervous system, has analogous activities in the periphery (p. 740). Signalling between VGLUT2-expressing neurons and NMDA receptor-expressing Schwann cells directs both formation and maintenance of the piloneural collar in mice. In conditional VGLUT2 mutants, the Schwann cells are disorganised and overall collar structure is severely disrupted. Moreover, treating the skin of adult mice with an NMDA receptor antagonist impairs touch-evoked responses, demonstrating defects in piloneural collar activity. Thus, continuous glutamate signalling between neurons and Schwann cells in the piloneural collar of the skin is essential for the integrity and function of this elaborate mechanosensory structure.

FGF signalling: keeping migrating cells on track

In Drosophila embryos, the longitudinal muscle cells surrounding the gut – the caudal visceral mesoderm (CVM) – arise in the posterior mesoderm and migrate anteriorly to reach their destination where they differentiate. Although this represents the longest cell migration event of Drosophila embryogenesis, the signals directing it are poorly understood. On p. 699, Angelike Stathopoulos and colleagues identify the FGF ligands Pyramus and Thisbe as crucial guidance cues for the CVM, signalling via the Heartless receptor to promote proper migration. The researchers use detailed live imaging and cell tracking analyses to describe wild-type migration, and analyse the consequences of disrupting FGF signalling, revealing defects in migration speed, directionality and cell survival. Intriguingly, by manipulating both the levels and location of ligand expression, they provide evidence for synergistic effects of Pyramus and Thisbe, although the mechanistic basis of such synergism remains to be investigated. Together, these data establish a new system for studying collective cell migration, and suggest additional complexities in FGF ligand-receptor interactions and signalling.

Plus…

Patterning embryos with oscillations: structure, function and dynamics of the vertebrate segmentation clock

The segmentation clock is an oscillating genetic network thought to govern the rhythmic and sequential subdivision of the elongating body axis of the vertebrate embryo into somites. Recent work, reviewed here by Oates et al, has provided evidence for how the period of the segmentation clock is regulated and how this affects the anatomy of the embryo. See the Review article on p. 625

Myoblast fusion: lessons from flies and mice

The fusion of myoblasts into multinucleate syncytia plays a fundamental role in muscle development and function. Here, Abmayr and Pavlath review the molecular events that drive myoblast fusion in the Drosophila embryo, in developing and regenerating mouse muscle, and in cultured muscle cells. See the Review article on p. 641

CycA takes control of endoreplication

Endocycles – repeated rounds of DNA replication without intervening mitoses – are involved in several terminal differentiation events. In Drosophila, for example, endoreplication occurs during the terminal differentiation of mechanosensory bristles. Endocycles are thought not to involve mitotic cyclins but here (p. 547), Agnès Audibert, Michel Gho and colleagues overturn that view by showing that cyclin A (CycA), which was thought to function exclusively in mitosis in Drosophila, is involved in endoreplication in the bristle lineage. The researchers show that CycA accumulates during the last part of endoreplication. CycA loss- and gain-of-function both induce changes in the dynamics of endoreplication, they report, and reduce the number of endocycles. Finally, CycA is required for relocalisation of ORC2, a member of the pre-replication complex, to the heterochromatin. These and other data reveal that CycA oscillations regulate endocycle dynamics in the fly mechanosensory bristle lineage and suggest that endoreplication involves remodelling of the entire cell-cycle network rather than simply a restriction of the canonical cell cycle as previously suggested.

Plane fact: aPKC orientates mitotic spindles

Mitotic spindle orientation, which is essential for epithelial morphogenesis and tissue maintenance, involves interactions between cortical polarity components and astral microtubules. The molecular machinery that regulates spindle apicobasal orientation during asymmetric cell division is well understood but what orientates the spindle along the epithelial plane in symmetrically dividing epithelial cells? On p. 503, Rui Gonçalo Martinho and colleagues provide the first in vivo evidence that atypical protein kinase C (aPKC) is involved in this process. Using a temperature-sensitive aPKC allele, the researchers show that Drosophila aPKC is required in imaginal discs for spindle planar orientation and for apical exclusion of Pins, a component of the molecular machinery that links the cell cortex to the astral microtubules. Apically localized aPKC is important for spindle planar orientation in mammalian epithelial cells in tissue culture; thus, these new observations suggest that the cortical cues required for spindle planar orientation are conserved between Drosophila and mammalian cells and are similar to those required for spindle orientation during asymmetric cell division.

pecanex wraps Notch up

During early development of the Drosophila nervous system, Notch signalling limits neuroblast numbers by preventing the cells that neighbour neuroblasts from also choosing a neuroblast fate. Disruption of Notch signalling prevents this ‘lateral inhibition’ and produces hyperplasias of the embryonic nervous system. The absence of pecanex (pcx), which encodes a conserved multi-pass transmembrane protein of unknown function, also causes a similar neurogenic phenotype. Now, Kenji Matsuno and colleagues propose that Pcx is a novel component of the Notch signalling pathway in Drosophila (see p. 558). They show that Pcx resides in the endoplasmic reticulum (ER) and is required upstream of activated Notch. Disruption of pcx function, they report, results in ER enlargement. However, hyper-induction of the unfolded protein response in the absence of pcx suppresses both ER enlargement and the development of a neurogenic phenotype. Together, these results suggest that the ER plays a previously unrecognised role in Notch signalling that involves Notch folding and that this ER function depends on pcx activity.

Wnt signalling regulates ciliogenesis

In zebrafish embryos, motile cilia lining the Kupffer’s vesicle (KV; the fish equivalent of the mouse node) help to establish left-right (LR) asymmetry. Wnt/β-catenin signalling is also involved in this process but precisely how it functions is unclear. Xueying Lin and colleagues now reveal that Wnt/β-catenin signalling directly regulates ciliogenesis in the zebrafish KV (see p. 514). The researchers show that reduced Wnt signalling disrupts LR patterning and ciliogenesis and downregulates Foxj1, a transcription factor that is required for the biosynthesis of motile cilia. KV-specific expression of foxj1a, they report, requires the presence of putative Lef1/Tcf binding sites in the foxj1a enhancer region, which suggests that Wnt signalling activates fox1ja transcription directly. Importantly, reduction of Wnt signalling also impairs foxj1 expression and ciliogenesis in developing zebrafish pronephric ducts and otic vesicles, epithelial structures that require Wnt activity for their development and function. The researchers propose, therefore, that the regulation of Foxj1 expression and ciliogenesis by Wnt/β-catenin signalling is a general developmental mechanism in zebrafish.

Egg cell orchestrates gametophyte development

Plant germ cells develop in specialised haploid structures called gametophytes. The female gametophyte of flowering plants contains an egg cell (which develops into the embryo), a central cell (which generates the endosperm that nurtures the embryo) and two accessory cell types, but what coordinates the development of these different cell types? On p. 498, Rita Groß-Hardt and co-workers report that egg-cell signalling mediated by LACHESIS (LIS), which encodes a homologue of a yeast pre-RNA splicing factor, regulates the development of Arabidopsis female gametophytic cells. lis mutants form supernumerary egg cells at the expense of accessory cells. The researchers now show that reducing LIS transcript levels specifically in the egg cell affects all the gametophyte cell types, which suggests that the egg cell orchestrates gametophyte differentiation. Notably, reduced LIS transcript levels in the egg cell interfere with homotypic nuclei fusion in the central cell and, consequently, endosperm formation. Thus, LIS-mediated egg-cell signalling ensures that endosperm only forms in the presence of a functional egg cell.

DAZL takes heat off testes

Mammalian testes are usually located outside the body cavity to ensure that the male germ cells are maintained at a low enough temperature to develop properly. If the testes get too warm, heat stress can cause germ cell apoptosis, which reduces fertility. Now, on p. 568, Kunsoo Rhee and co-workers reveal a cellular mechanism that protects male germ cells from heat stress. The researchers show that brief exposure of mouse testes to the core body temperature induces the assembly of stress granules (SGs; non-membranous cytoplasmic particles that contain translationally inert messenger ribonucleoproteins) in male germ cells. DAZL, a germ cell-specific translational regulator, translocates to SGs upon heat stress, they report, and is essential for their assembly. Importantly, DAZL-containing SGs sequester specific signalling molecules, such as RACK1 (receptor for activated protein kinase C), thereby blocking the apoptotic MAPK pathway. Together, these results suggest that DAZL is an essential component of SGs and that SGs prevent male germ cells from undergoing apoptosis upon heat stress.

Plus…

New for this year: poster articles!

Cilia in vertebrate development and disease

A taste of TGFβ in Tuscany

Regulation of DNA replication during development