Development Of Multicellular Animals Research Articles

Chromatin profiling identifies putative dual roles for H3K27me3 in regulating transposons and cell type-specific genes in choanoflagellates.

Gene expression is tightly controlled during animal development to allow the formation of specialized cell types. Our understanding of how animals evolved this exquisite regulatory control remains elusive, but evidence suggests that changes in chromatin-based mechanisms may have contributed. To investigate this possibility, here we examine chromatin-based gene regulatory features in the closest relatives of animals, choanoflagellates. Using Salpingoeca rosetta as a model system, we examined chromatin accessibility and histone modifications at the genome scale and compared these features to gene expression. We first observed that accessible regions of chromatin are primarily associated with gene promoters and found no evidence of distal gene regulatory elements resembling the enhancers that animals deploy to regulate developmental gene expression. Remarkably, a histone modification deposited by polycomb repressive complex 2, histone H3 lysine 27 trimethylation (H3K27me3), appeared to function similarly in S. rosetta to its role in animals, because this modification decorated genes with cell type-specific expression. Additionally, H3K27me3 marked transposons, retaining what appears to be an ancestral role in regulating these elements. We further uncovered a putative new bivalent chromatin state at cell type-specific genes that consists of H3K27me3 and histone H3 lysine 4 mono-methylation (H3K4me1). Together, our discoveries support the scenario that gene-associated histone modification states that underpin development emerged before the evolution of animal multicellularity.

Origin and evolution of animal multicellularity in the light of phylogenomics and cancer genetics

The rise of animals represents a major but enigmatic event in the evolutionary history of life. In recent years, numerous studies have aimed at understanding the genetic basis of this transition. However, genome comparisons of diverse animal and protist lineages suggest that the appearance of gene families that were previously considered animal specific indeed preceded animals. Animals’ unicellular relatives, such as choanoflagellates, ichthyosporeans, and filastereans, demonstrate complex life cycles including transient multicellularity as well as genetic toolkits for temporal cell differentiation, cell-to-cell communication, apoptosis, and cell adhesion. This has warranted further exploration of the genetic basis underlying transitions in cellular organization. An alternative model for the study of transitions in cellular organization is tumors, which exploit physiological programs that characterize both unicellularity and multicellularity. Tumor cells, for example, switch adhesion on and off, up- or downregulate specific cell differentiation states, downregulate apoptosis, and allow cell migration within tissues. Here, we use insights from both the fields of phylogenomics and tumor biology to review the evolutionary history of the regulatory systems of multicellularity and discuss their overlap. We claim that while evolutionary biology has contributed to an increased understanding of cancer, broad investigations into tissue—normal and transformed—can also contribute the framework for exploring animal evolution.

Oldest-known Neoproterozoic carbon isotope excursion: Earlier onset of Neoproterozoic carbon cycle volatility

The Neoproterozoic Era (1000–541 Ma) is characterized by the largest negative carbon isotope excursions in Earth history. Younger Neoproterozoic excursions are well-documented on multiple continental margins and associated with major events including snowball Earth glaciations, ocean-atmosphere oxygenation, and the evolution of animal multicellularity. However, due to a large gap in carbon isotopes before 900 Ma, the onset of early Neoproterozoic carbon cycle volatility has heretofore been obscure. Here, we present a mid-amplitude, negative carbon isotope excursion with δ13C values reaching a nadir of ~ − 6‰ from the Majiatun Formation in the Dalian Basin of the North China Craton dated between 950 and 920 Ma. The whole-rock 87Sr/86Sr ratios of limestone and dolostone are as low as ~0.7055, which is compatible with the Tonian age of the global carbonate curve. Identification of the Majiatun anomaly thus fills the critical gap in carbon isotopes and implies the onset of Neoproterozoic carbon cycle volatility ~130 m.y. earlier than previously thought. Now 5 negative carbon isotope excursions occur with increasing amplitude throughout Neoproterozoic time, implying deeper roots for the biogeochemical processes that may have causally led to late Neoproterozoic snowball glaciation, oxygenation, and biological innovation.

Integrin-Mediated Adhesion in the Unicellular Holozoan Capsaspora owczarzaki

In animals, cell-matrix adhesions are essential for cell migration, tissue organization, and differentiation, which have central roles in embryonic development [1-6]. Integrins are the major cell surface adhesion receptors mediating cell-matrix adhesion in animals. They are heterodimeric transmembrane proteins that bind extracellular matrix (ECM) molecules on one side and connect to the actin cytoskeleton on the other [7]. Given the importance of integrin-mediated cell-matrix adhesion in development of multicellular animals, it is of interest to discover when and how this machinery arose during evolution. Comparative genomic analyses have shown that core components of the integrin adhesome pre-date the emergence of animals [8-11]; however, whether it mediates cell adhesion in non-metazoan taxa remains unknown. Here, we investigate cell-substrate adhesion in Capsaspora owczarzaki, the closest unicellular relative of animals with the most complete integrin adhesome [11, 12]. Previous work described that the life cycle of C.owczarzaki (hereafter, Capsaspora) includes three distinct life stages: adherent; cystic; and aggregative [13]. Using an adhesion assay, we show that, during the adherent life stage, C.owczarzaki adheres to surfaces using actin-dependent filopodia. We show that integrin β2 and its associated protein vinculin localize as distinct patches in the filopodia. We also demonstrate that substrate adhesion and integrin localization are enhanced by mammalian fibronectin. Finally, using a specific antibody for integrin β2, we inhibited cell adhesion to a fibronectin-coated surface. Our results suggest that adhesion to the substrate in C.owczarzaki is mediated by integrins. We thus propose that integrin-mediated adhesion pre-dates the emergence of animals.

Somatic maintenance impacts the evolution of mutation rate

BackgroundThe evolution of multi-cellular animals has produced a conspicuous trend toward increased body size. This trend has introduced at least two novel problems: an expected elevated risk of somatic disorders, such as cancer, and declining evolvability due to generally reduced population size, lower reproduction rate and extended generation time. Low population size is widely recognized to explain the high mutation rates in animals by limiting the presumed universally negative selection acting on mutation rates.ResultsHere, we present evidence from stochastic modeling that the direction and strength of selection acting on mutation rates is highly dependent on the evolution of somatic maintenance, and thus longevity, which modulates the cost of somatic mutations.ConclusionsWe argue that the impact of the evolution of longevity on mutation rates may have been critical in facilitating animal evolution.

Using Nanobodies to Study Protein Function in Developing Organisms.

Polyclonal and monoclonal antibodies have been invaluable tools to study proteins over the past decades. While indispensable for most biological studies including developmental biology, antibodies have been used mostly in fixed tissues or as binding reagents in the extracellular milieu. For functional studies and for clinical applications, antibodies have been functionalized by covalently fusing them to heterologous partners (i.e., chemicals, proteins or other moieties). Such functionalized antibodies have been less widely used in developmental biology studies. In the past few years, the discovery and application of small functional binding fragments derived from single-chain antibodies, so-called nanobodies, has resulted in novel approaches to study proteins during the development of multicellular animals in vivo. Expression of functionalized nanobody fusions from integrated transgenes allows manipulating proteins of interest in the extracellular and the intracellular milieu in a tissue- and time-dependent manner in an unprecedented manner. Here, we describe how nanobodies have been used in the field of developmental biology and look into the future to imagine how else nanobody-based reagents could be further developed to study the proteome in living organisms.

Revision of the Capsaspora genome using read mating information adjusts the view on premetazoan genome

The genome sequences of unicellular holozoans, the closest relatives to animals, are shedding light on the evolution of animal multicellularity, shaping the genetic contents of the putative premetazoans. However, the assembly quality of the genomes remains poor compared to the major model organisms such as human and fly. Improving the assembly is critical for precise comparative genomics studies and further molecular biological studies requiring accurate sequence information such as enhancer analysis and genome editing. In this report, we present a new strategy to improve the assembly by fully exploiting the information of Illumina mate-pair reads. By visualizing the distance and orientation of the mapped read pairs, we could highlight the regions where possible assembly errors exist in the genome sequence of Capsaspora, a lineage of unicellular holozoans. Manual modification of these errors repaired 590 assembly problems in total and reassembled 84 supercontigs into 55. Our telomere prediction analysis using the read pairs containing the pan-eukaryotic telomere-like sequence identified at least 13 chromosomes. The resulting new assembly posed us a re-annotation of 112 genes, including 15 putative receptor protein tyrosine kinases. Our strategy thus provides a useful approach for improving assemblies of draft genomes, and the new Capsaspora genome offers us an opportunity to adjust the view on the genome of the unicellular animal ancestor.

Animal origins and the Tonian Earth system.

The Neoproterozoic Era (1000-541 million years ago, Ma) was characterized by dramatic environmental and evolutionary change, including at least two episodes of extensive, low-latitude glaciation, potential changes in the redox structure of the global ocean, and the origin and diversification of animal life. How these different events related to one another remains an active area of research, particularly how these environmental changes influenced, and were influenced by, the earliest evolution of animals. Animal multicellularity is estimated to have evolved in the Tonian Period (1000-720 Ma) and represents one of at least six independent acquisitions of complex multicellularity, characterized by cellular differentiation, three-dimensional body plans, and active nutrient transport. Compared with the other instances of complex multicellularity, animals represent the only clade to have evolved from wall-less, phagotrophic flagellates, which likely placed unique cytological and trophic constraints on the evolution of animal multicellularity. Here, we compare recent molecular clock estimates with compilations of the chromium isotope, micropaleontological, and organic biomarker records, suggesting that, as of now, the origin of animals was not obviously correlated to any environmental-ecological change in the Tonian Period. This lack of correlation is consistent with the idea that the evolution of animal multicellularity was primarily dictated by internal, developmental constraints and occurred independently of the known environmental-ecological changes that characterized the Neoproterozoic Era.

Transfection of Capsaspora owczarzaki, a close unicellular relative of animals.

ABSTRACTHow animals emerged from their unicellular ancestor remains a major evolutionary question. New genome data from the closest unicellular relatives of animals have provided important insights into the evolution of animal multicellularity. We know that the unicellular ancestor of animals had an unexpectedly complex genetic repertoire, including many genes that are key to animal development and multicellularity. Thus, assessing the function of these genes among unicellular relatives of animals is key to understanding how they were co-opted at the onset of the Metazoa. However, such analyses have been hampered by the lack of genetic tools. Progress has been made in choanoflagellates and teretosporeans, two of the three lineages closely related to animals, whereas no tools are yet available for functional analysis in the third lineage: the filastereans. Importantly, filastereans have a striking repertoire of genes involved in transcriptional regulation and other developmental processes. Here, we describe a reliable transfection method for the filasterean Capsaspora owczarzaki. We also provide a set of constructs for visualising subcellular structures in live cells. These tools convert Capsaspora into a unique experimentally tractable organism to use to investigate the origin and evolution of animal multicellularity.

The Diversification of Early Emerging Metazoans: A Window into the Evolution of Animal Multicellularity.

The biannual international workshop entitled "The diversification of early emerging metazoans: A window into animal evolution?" took place at the Evangelische Akademie Tutzing, Germany, 11-14. September 2017. It was organized by Thomas Bosch (Kiel), Thomas Holstein (Heidelberg), and Ulrich Technau (Vienna), and it was sponsored by the Deutsche Forschungsgemeinschaft (DFG). The meeting gathered over 140 researchers to discuss the contribution of non-bilaterian metazoan models (Porifera, Ctenophora, Placozoa, and Cnidaria) to our understanding of: a. The evolution of metazoan developmental processes; b. Fundamental molecular mechanisms underlying metazoan features; and c. The complex interactions that animals establish with their environment.

Phosphotyrosine signalling and the origin of animal multicellularity.

The evolution of multicellular animals (i.e. metazoans) from a unicellular ancestor is one of the most important yet least understood evolutionary transitions. Historically, given its indispensable functions in intercellular communication and exclusive presence in metazoans, phosphotyrosine (pTyr) signalling was considered a metazoan-specific evolutionary innovation that might have contributed to the origin of metazoan multicellularity. However, recent studies have led to a new understanding of pTyr signalling evolution and its role in the metazoan origin. Sequence analyses have unravelled a much earlier emergence of pTyr signalling in eukaryotic evolution. Even so, several distinct properties of holozoan pTyr signalling may have paved the way for a hypothesized functional transition of pTyr signalling at the multicellular origin, from environmental sensing to intercellular communication, and for it to evolve as a powerful intercellular signalling system for multicellularity. Biochemical analyses of premetazoan pTyr signalling components have further revealed the premetazoan origin of many key features of metazoan pTyr signalling, and the metazoan establishment of others, including the Csk-mediated negative regulation of the activity of Src, a conserved tyrosine kinase in the Holozoa. Finally, potential future directions are discussed, with a stress on the biological functions of premetazoan pTyr signalling via newly developed gene manipulation tools in non-animal holozoans.

Ediacaran stromatolites and intertidal phosphorite of the Salitre Formation, Brazil: Phosphogenesis during the Neoproterozoic Oxygenation Event

The Ediacaran Nova America and Gabriel members of the Salitre Formation are composed of limestone and economic phosphorite that accumulated on an unrimmed epeiric ramp along the margins of the Irecê Basin, Brazil. Deposition occurred during a marine transgression punctuated by higher-order fluctuations in relative sea-level that produced m-scale, shallowing-upward peritidal cycles. Cycles consist of six lithofacies rich in microbial sedimentary structures including subtidal, cross-stratified grainstones and hemispheroidal columnar stromatolite reefs overlain by intertidal flat sediments indicative of decreasing accommodation. Phosphorite is restricted to the paleocoast where digitate stromatolite biostromes colonized tidal flats.Phosphorite accumulation is interpreted to have been associated with biostromes because photosynthetic oxygen production created a redox gradient beneath the seafloor that phosphogenic chemosynthetic bacteria exploited. The concentration of francolite or sedimentary apatite in microbial laminae suggests these bacteria actively stored, released, and concentrated phosphate to promote in situ precipitation. The sealing effect of interbedded, fine-grained tidal deposits was also critical for maintaining the high levels of pore water phosphate required. The absence of francolite in subtidal columnar stromatolite reefs implies phosphogenesis was prevented in deeper, more energetic environments because wave pumping of oxygenated seawater through reefs surrounded by constantly moving grainy sediment promoted the recycling of P directly back to the water column.The Salitre Formation has a complex paragenesis, including hydrothermal alteration that produced Mississippi Valley-type Pb-Zn mineralization. δ18O values of Nova America member dolomites range from −10.2‰ to −0.5‰ (mean=−3.9‰) and δ13C ranges from −9.2‰ to +10.0‰ (mean=+2.8‰). Samples contain varying proportions of low-Mg calcite and saddle dolomite. δ18O values of hydrothermal veins range from −4.7‰ to −3.0‰ (mean=−4.2‰) reflecting equilibration with temperatures >80°C. δ13C values are between −7.0‰ and +5.6‰ (mean=−1.8‰,). Late lateritic weathering produced calcretes with δ18O values between −3.3‰ and −1.3‰, and δ13C values from −9.2‰ to −8.0‰ (mean values are −1.8‰ and −8.7‰, respectively). Petrographic analysis, generally low δ18O, and high δ13C values suggest hydrothermal dolomitization and remobilization of P led to secondary phosphate mineralization of intertidal stromatolite biostromes to produce economic phosphorite.Collectively, these results suggest that the benthic P-cycle in the Neoproterozoic was more complex than previously surmised and emphasize the multifaceted significance of microbial, paleoenvironmental, and diagenetic processes that allowed phosphorite to accumulate on the São Franciscan craton. Such information further elucidates attributes of the onset of Earth's second major phosphogenic episode, which is roughly coincident with the Neoproterozoic Oxygenation Event (NOE) and the evolution of multicellular animals.

The Birth of Animal Development: Multicellularity and the Germline.

The evolution of multicellular animals has been attributed to many kinds of selective advantage; here I suggest that the evolution of somatic cells to feed and protect the germline was central to the appearance of animals. This would have been driven by selection for extreme anisogamy--the evolution of sperm and egg. Evidence is adduced from the germline stem cells of simple animals (defining germline as any cell that normally produces the next generation via the sexual process) and from the control circuitry ubiquitous in animal germlines. With the soma and its elaboration came animal development, as we understand it.

MicroRNA evolution, expression, and function during short germband development in Tribolium castaneum.

MicroRNAs are well-established players in the development of multicellular animals. Most of our understanding of microRNA function in arthropod development comes from studies in Drosophila. Despite their advantages as model systems, the long germband embryogenesis of fruit flies is an evolutionary derived state restricted to several holometabolous insect lineages. MicroRNA evolution and expression across development in animals exhibiting the ancestral and more widespread short germband mode of embryogenesis has not been characterized. We sequenced small RNA libraries of oocytes and successive intervals covering the embryonic development of the short germband model organism, Tribolium castaneum. We analyzed the evolution and temporal expression of the microRNA complement and sequenced libraries of total RNA to investigate the relationships with microRNA target expression. We show microRNA maternal loading and sequence-specific 3′ end nontemplate oligoadenylation of maternally deposited microRNAs that is conserved between Tribolium and Drosophila. We further uncover large clusters encoding multiple paralogs from several Tribolium-specific microRNA families expressed during a narrow interval of time immediately after the activation of zygotic transcription. These novel microRNAs, together with several early expressed conserved microRNAs, target a significant number of maternally deposited transcripts. Comparison with Drosophila shows that microRNA-mediated maternal transcript targeting is a conserved process in insects, but the number and sequences of microRNAs involved have diverged. The expression of fast-evolving and species-specific microRNAs in the early blastoderm of T. castaneum is consistent with previous findings in Drosophila and shows that the unique permissiveness for microRNA innovation at this stage is a conserved phenomenon.

Reproduction, symbiosis, and the eukaryotic cell

This paper develops a conceptual framework for addressing questions about reproduction, individuality, and the units of selection in symbiotic associations, with special attention to the origin of the eukaryotic cell. Three kinds of reproduction are distinguished, and a possible evolutionary sequence giving rise to a mitochondrion-containing eukaryotic cell from an endosymbiotic partnership is analyzed as a series of transitions between each of the three forms of reproduction. The sequence of changes seen in this “egalitarian” evolutionary transition is compared with those that apply in “fraternal” transitions, such as the evolution of multicellularity in animals.

Symmetry transformations in ontogeny and evolution

Symmetry transformations are fundamental phenomena in the development and evolution of multicellular animals. Symmetry transformations at the cellular level during oogenesis and early development determine the basic axes of the future body, whereas the scale of these transformations is reduced in further development. In addition to the classical symmetry types, such as rotational (radial), mirror (bilateral), and translational symmetries, characteristic of biological processes is scale symmetry (self-similarity symmetry). The chaos is growing during fractal morphogenesis and other manifestations of fluctuating asymmetry. Biological symmetry and other variants of morphofunctional iterations are an effective way of morphogenesis via iteration of genetic programs.

Bacterial influences on animal origins.

Animals evolved in seas teeming with bacteria, yet the influences of bacteria on animal origins are poorly understood. Comparisons among modern animals and their closest living relatives, the choanoflagellates, suggest that the first animals used flagellated collar cells to capture bacterial prey. The cell biology of prey capture, such as cell adhesion between predator and prey, involves mechanisms that may have been co-opted to mediate intercellular interactions during the evolution of animal multicellularity. Moreover, a history of bacterivory may have influenced the evolution of animal genomes by driving the evolution of genetic pathways for immunity and facilitating lateral gene transfer. Understanding the interactions between bacteria and the progenitors of animals may help to explain the myriad ways in which bacteria shape the biology of modern animals, including ourselves.

Non-canonical Notch signaling represents an ancestral mechanism to regulate neural differentiation.

BackgroundCellular differentiation is a critical process during development of multicellular animals that must be tightly controlled in order to avoid precocious differentiation or failed generation of differentiated cell types. Research in flies, vertebrates, and nematodes has led to the identification of a conserved role for Notch signaling as a mechanism to regulate cellular differentiation regardless of tissue/cell type. Notch signaling can occur through a canonical pathway that results in the activation of hes gene expression by a complex consisting of the Notch intracellular domain, SuH, and the Mastermind co-activator. Alternatively, Notch signaling can occur via a non-canonical mechanism that does not require SuH or activation of hes gene expression. Regardless of which mechanism is being used, high Notch activity generally inhibits further differentiation, while low Notch activity promotes differentiation. Flies, vertebrates, and nematodes are all bilaterians, and it is therefore unclear if Notch regulation of differentiation is a bilaterian innovation, or if it represents a more ancient mechanism in animals.ResultsTo reconstruct the ancestral function of Notch signaling we investigate Notch function in a non-bilaterian animal, the sea anemone Nematostella vectensis (Cnidaria). Morpholino or pharmacological knockdown of Nvnotch causes increased expression of the neural differentiation gene NvashA. Conversely, overactivation of Notch activity resulting from overexpression of the Nvnotch intracellular domain or by overexpression of the Notch ligand Nvdelta suppresses NvashA. We also knocked down or overactivated components of the canonical Notch signaling pathway. We disrupted NvsuH with morpholino or by overexpressing a dominant negative NvsuH construct. We saw no change in expression levels for Nvhes genes or NvashA. Overexpression of Nvhes genes did not alter NvashA expression levels. Lastly, we tested additional markers associated with neuronal differentiation and observed that non-canonical Notch signaling broadly suppresses neural differentiation in Nematostella.ConclusionsWe conclude that one ancestral role for Notch in metazoans was to regulate neural differentiation. Remarkably, we found no evidence for a functional canonical Notch pathway during Nematostella embryogenesis, suggesting that the non-canonical hes-independent Notch signaling mechanism may represent an ancestral Notch signaling pathway.

Functions and Mechanisms of Fibroblast Growth Factor (FGF) Signalling in Drosophila melanogaster

Intercellular signalling via growth factors plays an important role in controlling cell differentiation and cell movements during the development of multicellular animals. Fibroblast Growth Factor (FGF) signalling induces changes in cellular behaviour allowing cells in the embryo to move, to survive, to divide or to differentiate. Several examples argue that FGF signalling is used in multi-step morphogenetic processes to achieve and maintain a transitional state of the cells required for the control of cell fate. In the genetic model Drosophila melanogaster, FGF signalling via the receptor tyrosine kinases Heartless (Htl) and Breathless (Btl) is particularly well studied. These FGF receptors affect gene expression, cell shape and cell–cell interactions during mesoderm layer formation, caudal visceral muscle (CVM) formation, tracheal morphogenesis and glia differentiation. Here, we will address the current knowledge of the biological functions of FGF signalling in the fly on the tissue, at a cellular and molecular level.

Signals That Trigger Dendrite Growth Are Identified

​HowHow does a dendrite grow? The answer to that question is central to understanding development of neurons, and thus to understanding entire nervous systems. But while the molecular signals underlying axon development have been relatively well described, comparatively little is known about the mechanisms of dendrite development, especially at its earliest stages. In this issue of PLoS Biology, Leonie Kirszenblat, Divya Pattabiraman, and Massimo Hilliard reveal a crucial role for a ligand-receptor pair that together coax the neuronal cell body to extend a dendrite toward its target. Development of the PQR oxygen sensory neuron in C. elegans proceeds with emergence of the dendrite from the posterior (right) side of the cell, as it senses an attractive source of ligand (Wnt molecule). The authors studied the so-called PQR neuron of the roundworm, C. elegans. PQR is an oxygen-sensing neuron located in the rear of the animal. One feature that makes it a good candidate for the study of neuronal development is its structural simplicity—it forms a single axon and a single dendrite, without the extensive branching that gives dendrites their name. Even more important for the current study, the neuron arises from its precursors post-embryonically, in the very early larval stage just after hatching, allowing the investigators to more easily observe influences on its development. The members of the Wnt family of proteins are well known signaling molecules, and are important determinants of development in multicellular animals, and so the authors sought Wnt mutants that altered dendrite development. They identified one, called LIN-44, which, when mutated, led to shortened, absent, or misrouted dendrites, while having no effect on axons. LIN-44 had been previously shown to play roles in regulating neuronal polarity, axon guidance, and synapse formation. LIN-44 is produced not in the PQR neuron itself, but in cells in the tail near the final location of the PQR dendrite. This suggested that the dendrite may use LIN-44 as a target for its growth, thus serving an “instructive” role in dendrite growth. But an alternative possibility was that LIN-44 plays only a “permissive” role, merely triggering the dendrite to grow, while some other factor tells it where to go. To distinguish between these, the authors expressed LIN-44 in more anterior regions. When they did, the dendrite grew toward the head of the worm, indicating LIN-44 provided instruction, not just permission, for the growing dendrite. That instructional signal is laid down early, even before the PQR cell itself appears. Even if the LIN-44 secreting cells were ablated shortly before PQR was born (while presumably leaving secreted LIN-44 in the surrounding tissue), the neuron still developed normally. But if expression of LIN-44 was delayed until after the dendrite began to grow, growth was abnormal, confirming the need for an early signal to the neuronal cell body. LIN-17 is a known receptor for LIN-44, and mutation of LIN-17 created dendrite developmental defects similar to those of its ligand, indicating the two act in a single pathway. The authors found that LIN-17 was expressed weakly but ubiquitously on the neuronal membrane before dendrite outgrowth, which they suggest may help the neuron detect the directional signal from LIN-44. Another Wnt ligand, EGL-20, also participates in the dendrite development process alongside LIN-44, and genetic evidence indicates it may interact with LIN-17 as well. Understanding these fundamental mechanisms of neuronal development may have practical, as well as theoretical, implications. Being able to control dendritic growth may be important for growing neurons from stem cells, which could find use in treatment of neurologic diseases such as spinal cord injury. Kirszenblat L, Pattabiraman D, Hilliard MA (2011) LIN-44/Wnt Directs Dendrite Outgrowth through LIN-17/Frizzled in C. elegans Neurons. doi:10.1371/journal.pbio.1001157