Anatomical Patterning Research Articles

Innate immunity in Aedes mosquitoes: from pathogen resistance to shaping the microbiota.

Discussions of host-microbe interactions in mosquito vectors are frequently dominated by a focus on the human pathogens they transmit (e.g. Plasmodium parasites and arboviruses). Underlying the interactions between a vector and its transmissible pathogens, however, is the physiology of an insect living and interacting with a world of bacteria and fungi including commensals, mutualists and primary and opportunistic pathogens. Here we review what is known about the bacteria and fungi associated with mosquitoes, with an emphasis on the members of the Aedes genus. We explore the reciprocal effects of microbe on mosquito, and mosquito on microbe. We analyse the roles of bacterial and fungal symbionts in mosquito development, their effects on vector competence, and their potential uses as biocontrol agents and vectors for paratransgenesis. We explore the compartments of the mosquito gut, uncovering the regionalization of immune effectors and modulators, which create the zones of resistance and immune tolerance with which the mosquito host controls and corrals its microbial symbionts. We examine the anatomical patterning of basally expressed antimicrobial peptides. Finally, we review the relationships between inducible antimicrobial peptides and canonical immune signalling pathways, comparing and contrasting current knowledge on each pathway in mosquitoes to the model insect Drosophila melanogaster. This article is part of the theme issue 'Sculpting the microbiome: how host factors determine and respond to microbial colonization'.

A Novel Perspective on Neuronal Control of Anatomical Patterning, Remodeling, and Maintenance.

While the nervous system may be best known as the sensory communication center of an organism, recent research has revealed a myriad of multifaceted roles for both the CNS and PNS from early development to adult regeneration and remodeling. These systems work to orchestrate tissue pattern formation during embryonic development and continue shaping pattering through transitional periods such as metamorphosis and growth. During periods of injury or wounding, the nervous system has also been shown to influence remodeling and wound healing. The neuronal mechanisms responsible for these events are largely conserved across species, suggesting this evidence may be important in understanding and resolving many human defects and diseases. By unraveling these diverse roles, this paper highlights the necessity of broadening our perspective on the nervous system beyond its conventional functions. A comprehensive understanding of the complex interactions and contributions of the nervous system throughout development and adulthood has the potential to revolutionize therapeutic strategies and open new avenues for regenerative medicine and tissue engineering. This review highlights an important role for the nervous system during the patterning and maintenance of complex tissues and provides a potential avenue for advancing biomedical applications.

COMPARISON AND CORRELATION BETWEEN MANDIBULAR ANTEGONIAL NOTCH DEPTH AND RAMUS MORPHOLOGY AMONG DIFFERENT PATTERNS OF GROWTH IN SKELETAL CLASS I, II AND III MALOCCLUSION SUBJECTS: AN OBSERVATIONAL STUDY

Objective: To provide a comprehensive comparison and correlation of these indicators among all skeletal patterns. Methodology: A total of 180 lateral cephalograms (81 males, 99 females) of patients between ages 18 to 25 years, were distributed equally (60 each) among class I, II, and III malocclusion groups in this observational study conducted at AFID, Rawalpindi. These were further sub-grouped (20 each) as average, horizontal and vertical growth patterns based on Jarabak’s ratio. Results: The AND was considerably deep in class I and class II vertical growers (p < 0.01) than in average and horizontal growers. Also, RH values were greatest for class I and class II horizontal growers (p < 0.05). In class I vertical group, a strong relationship between RH and RW (r=0.521) was observed. In class II horizontal group, AND showed a negative correlation with RH (r= -0.520) and RW (r= -0.516). In class III average group, RW was significantly correlated with RH (r=0.50) and AND (r=0.489). Conclusion: Vertical growers manifested the greatest AND values contrasted to both average and horizontal growers except class III subjects. Ramal height and width measurements were greatest in horizontal growers as opposed to the other two forms. Also, correlation exists between mandibular morphology and growth pattern. Thus, a thorough knowledge of varying mandibular anatomical patterning for all malocclusion groups is essential for diagnosis and treatment planning.

The Long and Winding Road-Vestibular Efferent Anatomy in Mice.

The precise functional role of the Efferent Vestibular System (EVS) is still unclear, but the auditory olivocochlear efferent system has served as a reasonable model on the effects of a cholinergic and peptidergic input on inner ear organs. However, it is important to appreciate the similarities and differences in the structure of the two efferent systems, especially within the same animal model. Here, we examine the anatomy of the mouse EVS, from its central origin in the Efferent Vestibular Nucleus (EVN) of the brainstem, to its peripheral terminations in the vestibular organs, and we compare these findings to known mouse olivocochlear anatomy. Using transgenic mouse lines and two different tracing strategies, we examine central and peripheral anatomical patterning, as well as the anatomical pathway of EVS axons as they leave the mouse brainstem. We separately tag the left and right efferent vestibular nuclei (EVN) using Cre-dependent, adeno-associated virus (AAV)-mediated expression of fluorescent reporters to map their central trajectory and their peripheral terminal fields. We couple this with Fluro-Gold retrograde labeling to quantify the proportion of ipsi- and contralaterally projecting cholinergic efferent neurons. As in some other mammals, the mouse EVN comprises one group of neurons located dorsal to the facial genu, close to the vestibular nuclei complex (VNC). There is an average of just 53 EVN neurons with rich dendritic arborizations towards the VNC. The majority of EVN neurons, 55%, project to the contralateral eighth nerve, crossing the midline rostral to the EVN, and 32% project to the ipsilateral eighth nerve. The vestibular organs, therefore, receive bilateral EVN innervation, but without the distinctive zonal innervation patterns suggested in gerbil. Similar to gerbil, however, our data also suggest that individual EVN neurons do not project bilaterally in mice. Taken together, these data provide a detailed map of EVN neurons from the brainstem to the periphery and strong anatomical support for a dominant contralateral efferent innervation in mammals.

Nested information processing in the living world.

Living organisms create, copy, and make use of information, the content depending on the level of organization. In cells, a network of signal chain proteins regulates gene expression and other cell functions. Incoming information is encoded through signal reception, processed by the network, and decoded by the synthesis of new gene products and other biological functions. Signaling proteins represent nodes, and signal transmission proceeds via allosteric binding, chemical and structural modifications, synthesis, sequestering, and degradation. The induction of the gene caudal type homeobox 2 (CDX2) in the mammalian preimplantation embryo is outlined as a demonstration of this concept. CDX2 is involved in the decision of cells to enter the trophoblast lineage. Two signal chains are coordinated into an information processing model with the help of logic gates. The model introduces a formal structure that incorporates experimental and morphological data. Above the cell level, information flow relates to tissue formation and functioning, and whole cells play the role of network nodes. This is described for the anatomical patterning of bone with implications for bone formation and homeostasis. The information usage in cells and tissues is set into a context of the nervous system and the interaction of human individuals in societies, both established scenes of information processing.

Conserved LBL1-ta-siRNA and miR165/166-RLD1/2 modules regulate root development in maize.

Root system architecture and anatomy of monocotyledonous maize is significantly different from dicotyledonous model Arabidopsis The molecular role of non-coding RNA (ncRNA) is poorly understood in maize root development. Here, we address the role of LEAFBLADELESS1 (LBL1), a component of maize trans-acting short-interfering RNA (ta-siRNA), in maize root development. We report that root growth, anatomical patterning, and the number of lateral roots (LRs), monocot-specific crown roots (CRs) and seminal roots (SRs) are significantly affected in lbl1-rgd1 mutant, which is defective in production of ta-siRNA, including tasiR-ARF that targets AUXIN RESPONSE FACTOR3 (ARF3) in maize. Altered accumulation and distribution of auxin, due to differential expression of auxin biosynthesis and transporter genes, created an imbalance in auxin signalling. Altered expression of microRNA165/166 (miR165/166) and its targets, ROLLED1 and ROLLED2 (RLD1/2), contributed to the changes in lbl1-rgd1 root growth and vascular patterning, as was evident by the altered root phenotype of Rld1-O semi-dominant mutant. Thus, LBL1/ta-siRNA module regulates root development, possibly by affecting auxin distribution and signalling, in crosstalk with miR165/166-RLD1/2 module. We further show that ZmLBL1 and its Arabidopsis homologue AtSGS3 proteins are functionally conserved.

Cancer as a disorder of patterning information: computational and biophysical perspectives on the cancer problem

The current paradigm views cancer as arising clonally from degradation of genetic information in single cells. A complementary perspective, originating at the dawn of modern developmental biology, is that cancer is the result of system disorder of algorithms that normally orchestrate individual cell activities toward specific anatomical structures and away from tumorigenesis. A view of cancer as disease of geometry focuses on the pathways that allow cells to cooperate to build and maintain large-scale anatomical patterning. Cancer may result when cells stop maintaining higher-order structures and reduce the boundary of their computational selves to single-cell level, reverting to unicellular lifestyle in which the rest of the organism is merely part of the environment at the expense of which all living things survive. While this view has been widely discussed, little progress has been made in providing quantitative, mechanistic framework within which this perspective's specific and unique implications for treatment strategies can be tested and biomedically exploited. Here, we highlight two recent areas of progress which may facilitate much-needed progress on the cancer problem. First, we review the roles that endogenous bioelectrical networks, operating across many tissues in vivo, play as medium of information processing in tumor suppression, progression, and reprogramming. Second, we provide primer to the development of computational theory and tools for quantifying the information and causal control structures in cancer and other complex biological systems. Rigorous mathematical formalisms now exist to measure and analyze the extent to which a whole is more than the sum of its parts, applications of which could lead to new strategies for cancer reprogramming. Here, we review the basic landscape of these related subfields, and sketch specific ways in which synthesis of novel integrative biophysics and mathematical analysis may contribute to novel ways to understand and address cancer in vivo.

The molecular pathogenesis of morphoea: from genetics to future treatment targets.

A number of immunoinflammatory and profibrotic mechanisms are recognized in the pathogenesis of broad sclerotic skin processes and, more specifically, morphoea. However, the precise aetiopathogenesis is complex and remains unclear. Morphoea is clinically heterogeneous, with variable anatomical patterning, depth of tissue involvement and sclerotic, inflammatory, atrophic and dyspigmented morphology. Underlying mechanisms determining these reproducible clinical subsets are poorly understood but of great clinical and therapeutic relevance. Regional susceptibility mechanisms (e.g. environmental triggers, mosaicism and positional identity) together with distinct pathogenic determinants (including innate, adaptive and imbalanced pro- and antifibrotic signalling pathways) are likely implicated. In the age of genetic profiling and personalized medicine, improved characterization of the environmental, systemic, local, genetic and immunopathological factors underpinning morphoea pathogenesis may open the door to novel targeted therapeutic approaches.

HCN4 ion channel function is required for early events that regulate anatomical left-right patterning in a nodal and lefty asymmetric gene expression-independent manner.

ABSTRACTLaterality is a basic characteristic of all life forms, from single cell organisms to complex plants and animals. For many metazoans, consistent left-right asymmetric patterning is essential for the correct anatomy of internal organs, such as the heart, gut, and brain; disruption of left-right asymmetry patterning leads to an important class of birth defects in human patients. Laterality functions across multiple scales, where early embryonic, subcellular and chiral cytoskeletal events are coupled with asymmetric amplification mechanisms and gene regulatory networks leading to asymmetric physical forces that ultimately result in distinct left and right anatomical organ patterning. Recent studies have suggested the existence of multiple parallel pathways regulating organ asymmetry. Here, we show that an isoform of the hyperpolarization-activated cyclic nucleotide-gated (HCN) family of ion channels (hyperpolarization-activated cyclic nucleotide-gated channel 4, HCN4) is important for correct left-right patterning. HCN4 channels are present very early in Xenopus embryos. Blocking HCN channels (Ih currents) with pharmacological inhibitors leads to errors in organ situs. This effect is only seen when HCN4 channels are blocked early (pre-stage 10) and not by a later block (post-stage 10). Injections of HCN4-DN (dominant-negative) mRNA induce left-right defects only when injected in both blastomeres no later than the 2-cell stage. Analysis of key asymmetric genes' expression showed that the sidedness of Nodal, Lefty, and Pitx2 expression is largely unchanged by HCN4 blockade, despite the randomization of subsequent organ situs, although the area of Pitx2 expression was significantly reduced. Together these data identify a novel, developmental role for HCN4 channels and reveal a new Nodal-Lefty-Pitx2 asymmetric gene expression-independent mechanism upstream of organ positioning during embryonic left-right patterning.

Conserved roles for cytoskeletal components in determining laterality.

Consistently-biased left-right (LR) patterning is required for the proper placement of organs including the heart and viscera. The LR axis is especially fascinating as an example of multi-scale pattern formation, since here chiral events at the subcellular level are integrated and amplified into asymmetric transcriptional cascades and ultimately into the anatomical patterning of the entire body. In contrast to the other two body axes, there is considerable controversy about the earliest mechanisms of embryonic laterality. Many molecular components of asymmetry have not been widely tested among phyla with diverse bodyplans, and it is unknown whether parallel (redundant) pathways may exist that could reverse abnormal asymmetry states at specific checkpoints in development. To address conservation of the early steps of LR patterning, we used the Xenopus laevis (frog) embryo to functionally test a number of protein targets known to direct asymmetry in plants, fruit fly, and rodent. Using the same reagents that randomize asymmetry in Arabidopsis, Drosophila, and mouse embryos, we show that manipulation of the microtubule and actin cytoskeleton immediately post-fertilization, but not later, results in laterality defects in Xenopus embryos. Moreover, we observed organ-specific randomization effects and a striking dissociation of organ situs from effects on the expression of left side control genes, which parallel data from Drosophila and mouse. Remarkably, some early manipulations that disrupt laterality of transcriptional asymmetry determinants can be subsequently "rescued" by the embryo, resulting in normal organ situs. These data reveal the existence of novel corrective mechanisms, demonstrate that asymmetric expression of Nodal is not a definitive marker of laterality, and suggest the existence of amplification pathways that connect early cytoskeletal processes to control of organ situs bypassing Nodal. Counter to alternative models of symmetry breaking during neurulation (via ciliary structures absent in many phyla), our data suggest a widely-conserved role for the cytoskeleton in regulating left-right axis formation immediately after fertilization of the egg. The novel mechanisms that rescue organ situs, even after incorrect expression of genes previously considered to be left-side master regulators, suggest LR patterning as a new context in which to explore multi-scale redundancy and integration of patterning from the subcellular structure to the entire bodyplan.

Patterns in naevoid skin disease: development, disease and modelling

The aetiology of pattern-formation in human naevoid skin disease remains unknown. However, it is likely that the majority of previously proposed mechanisms - those that simply rely on passive clonal trafficking in embryogenesis - are incomplete. A more comprehensive explanation for pattern-formation in naevi invokes the principle of self-organization. We define two types of patterning: anatomical and functional. Anatomical patterning is where the abnormal clone is limited to regions of pathologic skin, while functional patterning is where the abnormal clone and pathologic skin are spatially uncorrelated. From a theoretical perspective self-organized naevoid patterns may be either secondary to local interactions between normal and aberrant genotypes or due to the interaction between aberrant genotypes and the presence of normal embryonic patterning cues. The latter possibility suggests the critical observation and analysis of patterns in naevoid skin disease may lead to unique insights into key aspects of early human embryogenesis.

LGI1-associated epilepsy through altered ADAM23-dependent neuronal morphology

Most epilepsy genes encode ion channels, but the LGI1 gene responsible for autosomal dominant partial epilepsy with auditory features produces a secreted protein. LGI1 is suggested to regulate PSD-95 via ADAM22. However, no unbiased screen of LGI1 action has been conducted. Here, we searched for brain genes supporting high affinity LGI-1 binding. ADAM23 was the only LGI1 interactor identified. The related proteins, ADAM22 and ADAM11, but not ADAM12, bind LGI1. Neither ADAM23 nor ADAM11, nor some forms of ADAM22, contain PDZ-interacting sequences, suggesting PSD-95-independent mechanisms in ADPEAF. Because ADAMs modulate integrins, we examined LGI1 effect on neurite outgrowth. LGI1 increases outgrowth from wild-type but not ADAM23−/− neurons. Furthermore, CA1 pyramidal neurons of ADAM23−/− hippocampi have reduced dendritic arborization. ADAM23−/− mice exhibit spontaneous seizures, while ADAM23+/− mice have decreased seizure thresholds. Thus, LGI1 binding to ADAM23 is necessary to correctly pattern neuronal morphology and altered anatomical patterning contributes to ADPEAF.

Anatomical fat patterning in male Nigerian soccer players

Soccer is the most popular sport in the world. Due to i ts global acclaim, a lot of scient ific studies have been undertaken on different aspects of the sport, particularly in Europe. Few studies have investigated patterns of body fat distribution in African soccer players, in general and patterns offat distribution of soccer players by playing positions, in particular. The purpose of this study was to determine the patterns of body fat distribution among Nigerian university soccer players and the possible effect of fat pattern on playing positions. Skinfold measurements were taken on 20 soccer players, using ISAK procedures. Results showed that the midfielders had the least (13.5 ± 3.7 %), while the goalkeepers had thehighest percentage body fat (16.8 ± 2.3 %). Skinfold values were found to vary by playing positions. Goalkeepers had the highest bicepsskinfold thickness (7.2 ± 2.8 mm). Supra-iliac skinfold thickness was least in the defenders (5.2 ± 0.4 mm) but highest in the midfielders (13.1 ±6.5mm). Chest and waist girths were least in the midfielders (86.5 ± 5.3 cm; 82.3 ± 3.6cm). It was concluded that the differences in anthropometricvariables among soccer players could be due to the demands of the playing posi tions. This view is, however, contestable in view of the present playing style requiring all players (except the goal keepers)to assume different playing posi tions in actual competi tion.

Anatomical Patterning of Visceral Adipose Tissue: Race, Sex, and Age Variation

We tested sex, race, and age differences in the patterning of visceral adipose tissue (VAT) and subcutaneous adipose tissue. Contiguous 1-cm-thick magnetic resonance (MR) images of the abdomen were collected from 820 African-American and white adults. Repeated-measures ANOVA was used to examine the effects of image location, sex, race, and age (>or=50 vs. <50 years) on adipose tissue areas. Maximum VAT area was identified for each subject from the raw data. Compared to women, men had greater total VAT volume (p < 0.0001), and their maximum VAT area occurred higher in the abdomen (p < 0.0001). Among white men, maximim VAT area most frequently occurred 5 to 10 cm above L4-L5, whereas in the other groups, maximim VAT area most frequently occurred 1 to 4 cm above L4-L5 (p < 0.0001). African-American men had greater total VAT volume than African-American women (p < 0.01), but this sex difference was only significant using single images cranial to L4-L5 + 2 cm. Age-related increases in VAT tended to be greatest 5 to 10 cm above L4-L5 in men and near L4-L5 in women. A single MR image 5 to 10 cm above L4-L5 may allow more accurate conclusions than the L4-L5 image regarding group differences in visceral adiposity.

Strategies to unravel molecular codes essential for the development of meso‐diencephalic dopaminergic neurons

Understanding the development of neuronal systems has become an important asset in the attempt to solve complex questions about neuropathology as found in Parkinson's disease, schizophrenia and other complex neuronal diseases. The development of anatomical and functional divergent structures in the brain is achieved by a combination of early anatomical patterning and highly coordinated neuronal migration and differentiation events. Fundamental to the existence of divergent structures in the brain is the early region-specific molecular programming. Neuronal progenitors located along the neural tube can still adapt many different identities. Their exact position in the developing brain, however, determines early molecular specification by region-specific signalling molecules. These signals determine time and region-specific expression of early regulatory genes, leading to neuronal differentiation. Here, we focus on a well-described neuronal group, the meso-diencephalic dopaminergic neurons, of which heterogeneity based on anatomical position could account for the difference in vulnerability of specific subgroups as observed in Parkinson's disease. The knowledge of their molecular coding helps us to understand how the meso-diencephalic dopaminergic system is built and could provide clues that unravel mechanisms associated with the neuropathology in complex diseases such as Parkinson's disease.

Radial leaves of the maize mutant ragged seedling2 retain dorsiventral anatomy

ragged seedling2 ( rgd2) is a novel, recessive mutation affecting lateral organ development in maize. The mutant phenotype of homozygous rgd2-R leaves is variable. Mild leaf phenotypes have a reduced midrib and may be moderately narrow and furcated; severe Rgd2-R − leaves are filamentous or even radial. Despite their radial morphology, severe Rgd2-R − mutant leaves develop distinct adaxial and abaxial anatomical features. Although Rgd2-R − mutants exhibit no reduction in adaxial or abaxial cell types, areas of epidermal cell swapping may occur that are associated with misaligned vascular bundles and outgrowths of ectopic margins. Scanning electron microscopy of young primordia and analyses of leaf developmental-marker gene expression in mutant apices reveal that RGD2 functions during recruitment of leaf founder cells and during expansive growth of leaf primordia. Overall, these phenotypes suggest that development is uncoordinated in Rgd2-R − mutant leaves, so that leaf components and tissues may develop quasi-independently. Models whereby RGD2 is required for developmental signaling during the initiation, anatomical patterning, and lateral expansion of maize leaves are discussed.

Vessels and Nerves: Marching to the Same Tune

The patterning of the nervous system is achieved through coordinated action of a variety of repulsive or attractive neuronal guidance factors that direct the growth of growing axons to specific pathways. Recent studies suggest that the same or similar sets of factors also guide migration of endothelial cells, helping to direct the stereotypical embryonic patterning of the developing vertebrate vascular system.

The neurovascular unit and its growth factors: coordinated response in the vascular and nervous systems

The nervous and vascular systems contain many common organizational features and develop similarly in terms of anatomical patterning. During embryogenesis and in regions of the brain undergoing postnatal neurogenesis, neural stem cells and endothelial cells are found in close proximity, or within a so-called vascular niche. The similarities in patterning and proximity may reflect coordinated development based on responsiveness to similar growth factors such as vascular endothelial growth factor, semaphorin, and ephrins/Ephs: molecules involved in the development and maintenance of both the nervous and vascular systems. Despite the blatant similarities between the vascular and nervous systems, little is still known about the co-dependence and/or interactions between the two systems during development and following alterations in metabolic demand as seen during aging, exercise, and disease processes. The interactions between the two systems involving common growth factors suggest these two systems have evolved in an interconnected way.

Angiogenic network formation in the developing vertebrate trunk.

We have used time-lapse multiphoton microscopy of living Tg(fli1:EGFP)y1 zebrafish embryos to examine how a patterned, functional network of angiogenic blood vessels is generated in the early vertebrate trunk. Angiogenic vascular sprouts emerge from the longitudinal trunk axial vessels (the dorsal aorta and posterior cardinal vein) in two spatially and temporally distinct steps. Dorsal aorta-derived sprouts form an initial primary network of vascular segments, followed by emergence of vein-derived secondary vascular sprouts that interact and interconnect dynamically with the primary network to initiate vascular flow. Using transgenic silent heart mutant embryos, we show that the gross anatomical patterning of this network of vessels does not require blood circulation. However, our results suggest that circulatory flow dynamics play an important role in helping to determine the pattern of interconnections between the primary network and secondary sprouts, and thus the final arterial or venous identity of the vessels in the functional network. We discuss a model to explain our results combining genetic programming of overall vascular architecture with hemodynamic determination of circulatory flow patterns.

Building the house around the plumbing

Signaling between growing blood vessels and the tissues that they innervate has traditionally been viewed as a one-way conversation, with organs and tissues supplying important cues for the growth and anatomical patterning of the blood vessels supplying them, but not vice-versa. Two recent papers1,2 now provide evidence that blood vessels can have an important role in promoting the assembly of organs and tissues. These papers show that proper formation of the pancreas1 and liver2 and induction of endocrine and hepatic cell types in these endodermal organs requires inductive signals from blood vessels. BioEssays 24:397–400, 2002. Published 2002 Wiley Periodicals, Inc.