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Abstract Autosomal Recessive Polycystic Kidney Disease (ARPKD) is a genetic disorder with an incidence of ~1:20,000 that manifests in a wide range of renal and liver disease severity in human patients and can lead to perinatal mortality. ARPKD is caused by mutations in PKHD1 , which encodes the large membrane protein, Fibrocystin, required for normal branching morphogenesis of the ureteric bud during embryonic renal development. The variation in ARPKD phenotype suggests that in addition to PKHD1 mutations, other genes may play a role, acting as modifiers of disease severity. One such pathway involves non-canonical Wnt/Planar Cell Polarity (PCP) signalling that has been associated with other cystic kidney diseases, but has not been investigated in ARPKD. Analysis of the Atmin Gpg6 mouse showed kidney, liver and lung abnormalities, suggesting it as a novel mouse tool for the study of ARPKD. Further, modulation of Atmin affected Pkhd1 mRNA levels, altered non-canonical Wnt/PCP signalling and impacted cellular proliferation and adhesion, although Atmin does not bind directly to the C-terminus of Fibrocystin. Differences in ATMIN and VANGL2 expression were observed between normal human paediatric kidneys and age-matched ARPKD kidneys. Significant increases in ATMIN , WNT5A , VANGL2 and SCRIBBLE were seen in human ARPKD versus normal kidneys; no substantial differences were seen in DAAM2 or NPHP2. A striking increase in E-cadherin was also detected in ARPKD kidneys. This work indicates a novel role for non-canonical Wnt/PCP signalling in ARPKD and suggests ATMIN as a modulator of PKHD1. Graphical abstract Unlabelled Image Highlights • The Atmin Gpg6 mouse displays kidney, liver and lung defects. • Atmin modulates Pkhd1 expression and affects cellular proliferation and adhesion in mIMCD3 cells. • Altered Wnt signalling is observed in Atmin/Pkhd1 knockdowns and in ARPKD kidneys. [ABSTRACT FROM AUTHOR]

We present a description of the external morphology of Phyllomedusa azurea and describe the internal oral morphology of P. azurea and P. oreades from populations of the Brazilian Cerrado. We also present a comparison with the available descriptions of the external morphology of tadpoles from the P. hypochondrialis group and review the internal oral morphology of the Phyllomedusa genus. The tadpole of P. azurea is characterized by a tooth row formula of 2(2)/3(1), few submarginal papillae, and spiracle positioned ventrally. Phyllomedusa oreades has a diamond-shaped buccal floor, numerous pustulations randomly distributed throughout the buccal floor arena, and a triangular buccal roof. The variation observed in the morphology of P. azurea tadpoles highlights the need to understand how morphological variation affects traits used in species diagnosis and the extent to which this variation could be explained by resource use, geographic variation, and/or ontogeny. [ABSTRACT FROM AUTHOR]

Abstract: Gene flow has historically been thought to constrain local adaptation; yet, recent research suggests that populations can diverge despite exchanging genes. Here I use a common garden experiment to assess the combined effects of gene flow and natural selection on morphological variation of 16 wood frog (Rana sylvatica) populations, a species known to experience divergent selection pressures in open‐ and closed‐canopy ponds across relatively small geographic scales. Wood frog tadpoles from different ponds showed significant morphological variation associated with canopy type with a trade‐off between tail length and body depth consistent with previous research. In contrast, neutral genetic differentiation of nine microsatellite loci as measured by Jost's D was not associated with canopy type, indicating no pattern of isolation by environment. Genetic structure analyses indicated some substructure across the 16 ponds (K = 4); however, three out of four assigned clusters included both open‐ and closed‐canopy ponds. Together, these results suggest that morphological divergence among these wood frog populations is occurring despite gene flow and that selection within these environments is strong. Furthermore, morphological variation among ponds differed across two sampling periods during larval development, demonstrating the importance of evaluating phenotypic divergence over multiple time periods and at a time relevant to the processes being studied. [ABSTRACT FROM AUTHOR]

Long-term data on the morphological anomalies of four anuran species (family Ranidae) and two tailed amphibian species (families Hynobiidae and Salamandridae), inhabiting forest and urbanized areas in the eastern slope of the Middle Urals, have been studied. The morphological deviations of amphibians were investigated in terms of the module principle, which predetermines the similarity of evolutionary transformations in different taxa and limit the number of possible directions of diversification in morphogenesis. The definitive spectra and frequencies of morphological anomalies in juvenile and adult individuals are compared in the urbanization gradient. Original methodological and methodical approaches to using the potential and implemented spectra of deviation are proposed for assessing the role of the ecological component in their formation. The possibility of using deviant forms of variability for assessing the evolutionary and adaptive potentials of the species is discussed. [ABSTRACT FROM AUTHOR]

The axolotl ( Ambystoma mexicanum ) has long been the subject of biological research, primarily owing to its outstanding regenerative capabilities. However, the gene expression programs governing its embryonic development are particularly underexplored, especially when compared to other amphibian model species. Therefore, we performed whole transcriptome polyA+ RNA sequencing experiments on 17 stages of embryonic development. As the axolotl genome is unsequenced and its gene annotation is incomplete, we built de novo transcriptome assemblies for each stage and garnered functional annotation by comparing expressed contigs with known genes in other organisms. In evaluating the number of differentially expressed genes over time, we identify three waves of substantial transcriptome upheaval each followed by a period of relative transcriptome stability. The first wave of upheaval is between the one and two cell stage. We show that the number of differentially expressed genes per unit time is higher between the one and two cell stage than it is across the mid-blastula transition (MBT), the period of zygotic genome activation. We use total RNA sequencing to demonstrate that the vast majority of genes with increasing polyA+ signal between the one and two cell stage result from polyadenylation rather than de novo transcription. The first stable phase begins after the two cell stage and continues until the mid-blastula transition, corresponding with the pre-MBT phase of transcriptional quiescence in amphibian development. Following this is a peak of differential gene expression corresponding with the activation of the zygotic genome and a phase of transcriptomic stability from stages 9–11. We observe a third wave of transcriptomic change between stages 11 and 14, followed by a final stable period. The last two stable phases have not been documented in amphibians previously and correspond to times of major morphogenic change in the axolotl embryo: gastrulation and neurulation. These results yield new insights into global gene expression during early stages of amphibian embryogenesis and will help to further develop the axolotl as a model species for developmental and regenerative biology. [ABSTRACT FROM AUTHOR]

Phenotypic flexibility of morphological characters is widespread in the animal kingdom. In the present paper, we investigated altitudinal variation in organ size (heart, lungs, livers, kidneys and digestive tract) in the spotlegged treefrog (Polypedates megacephalus) across three populations along an altitudinal gradient in southwestern China. Both heart and lung mass increased with altitude, and is possibly linked to a lower oxygen supply at high elevations; a higher liver mass suggested the increased need for energy stores. Despite significant differences between populations, we found no distinct cline in the length of the digestive tract according to altitude. [ABSTRACT FROM AUTHOR]

Adhesion differences are the main driver of cell sorting and related processes such as boundary formation or tissue positioning. In the early amphibian embryo, graded variations in cadherin density and localized expression of adhesion-modulating factors are associated with regional differences in adhesive properties including overall adhesion strength. The role of these differences in embryonic boundary formation has not been studied extensively, but available evidence suggests that adhesion strength differentials are not essential. On the other hand, the inside-out positioning of the germ layers is correlated with adhesion strength, although the biological significance of this effect is unclear. By contrast, the positioning of dorsal mesoderm tissues along the anterior-posterior body axis is essential for axis elongation, but the underlying sorting mechanism is not correlated with adhesion strength, and may rely on specific cell adhesion. Formation of the ectoderm-mesoderm boundary is the best understood sorting related process in the frog embryo. It relies on contact-induced cell repulsion at the tissue interface, driven by Eph-ephrin signaling and paraxial protocadherin-dependent self/non-self recognition. [ABSTRACT FROM AUTHOR]

Whilst many vertebrates appear externally left-right symmetric, the arrangement of internal organs is asymmetric. In zebrafish, the breaking of left-right symmetry is organised by Kupffer's Vesicle (KV): an approximately spherical, fluid-filled structure that begins to form in the embryo 10 hours post fertilisation. A crucial component of zebrafish symmetry breaking is the establishment of a cilia-driven fluid flow within KV. However, it is still unclear (a) how dorsal, ventral and equatorial cilia contribute to the global vortical flow, and (b) if this flow breaks left-right symmetry through mechanical transduction or morphogen transport. Fully answering these questions requires knowledge of the three-dimensional flow patterns within KV, which have not been quantified in previous work. In this study, we calculate and analyse the three-dimensional flow in KV. We consider flow from both individual and groups of cilia, and (a) find anticlockwise flow can arise purely from excess of cilia on the dorsal roof over the ventral floor, showing how this vortical flow is stabilised by dorsal tilt of equatorial cilia, and (b) show that anterior clustering of dorsal cilia leads to around 40 % faster flow in the anterior over the posterior corner. We argue that these flow features are supportive of symmetry breaking through mechano-sensory cilia, and suggest a novel experiment to test this hypothesis. From our new understanding of the flow, we propose a further experiment to reverse the flow within KV to potentially induce situs inversus. [ABSTRACT FROM AUTHOR]

Claudins are tetratransmembrane tight junction proteins and play important roles in regulating paracellular permeability of different nephron segments of the kidney. However, the roles of claudins in kidney development remain largely unknown. Here we studied the expression and functions of claudin-6 in Xenopus pronephros development. Xenopus claudin-6 is expressed in the developing pronephric tubule and duct but not glomus. Knockdown of claudin-6 by specific morpholino led to severe defects in pronephros tubular morphogenesis and blocked the terminal differentiation of the tubule cells. The claudin-6 morpholino targeted tubule cells showed failure of apical accumulation of actin and reduced lateral expression of tight junction protein Na/K-ATPase, suggesting an incomplete epithelization likely due to defected cell adhesions and apical-lateral polarity. Our work uncovered a novel role for claudin-6 in embryonic kidney development. [ABSTRACT FROM AUTHOR]

The duality of amphibians is epitomized by their pharyngeal arch skeletons, the larval and adult morphologies of which enable very different feeding and breathing behaviors in aquatic and terrestrial life. To accomplish this duality, amphibian pharyngeal arch skeletons undergo two periods of patterning: embryogenesis and metamorphosis, and two periods of growth: larval and postmetamorphic. Their extreme ontogenetic variation, however, is coupled with relatively limited phylogenetic variation, I propose that amphibians face an evolutionary tradeoff between their ontogenetic and phylogenetic diversification that stems from the need to grow and transform the pharyngeal arch skeleton in cartilage rather than bone. Cartilage differs fundamentally from bone in its histology, function, development and growth. Cartilage is also the first skeletal tissue to form embryonically and provides more cellular pathways for shape change than bone. This article combines morphological, histological and experimental perspectives to explore how pharyngeal arch cartilage shape is controlled in amphibian embryogenesis, growth and metamorphosis, and how amphibian skeletal ontogenies are impacted by using cartilage to evolve a complex life cycle and in evolving away from a complex life cycle. [ABSTRACT FROM AUTHOR]

Bidder's organ is an ovary-like structure, which develops from the anterior part of the gonadal ridge in anuran amphibians belonging to the Bufonidae family. Bidder's organs form in both males and females. Because Bidder's organ contains female germ cells (oocytes), the bufonid males are de facto hermaphrodites. Due to similarity with the undeveloped ovary. Bidder's organ was, in early literature, described, inaccurately, as a structure present only in males. Due to the fact that Bidder's organ is a unique structure present only in Bufonidae, it is not well studied and its function still remains a mystery. Here we describe the development and structure of Bidder's organs, summarize the knowledge on gene expression and steroidogenic activity in these organs, and present hypotheses regarding Bidder's organ function. [ABSTRACT FROM AUTHOR]

We describe a new species of Pseudopaludicola endemic to the Caatinga ecoregion of northeastern Brazil. The new species is characterized morphologically by small size, lack of T-shape terminal phalanges, smooth upper eyelids, presence of abdominal and vocal sac folds, light cream-colored vocal sac, and short hind limbs with tibia-tarsal articulation reaching the eye. The tadpole has a globular body shape, low tail fins, and a ventral oral disc bordered by a single row of marginal papillae with a wide anterior gap and two ventrolateral gaps; oral formula: 2(2)/2(l). The advertisement call consists of a well-defined sequence of notes comprising three nonconcatenated pulses, each with long interpulse intervals (111 ± 21 ms) and average note duration of 238 ± 31 ms. The mean dominant frequency is 5636 ± 300 Hz, and increases from the first to the last pulse in each note. The advertisement call easily distinguishes the new species from all other congeners for which calls are known. [ABSTRACT FROM AUTHOR]

Background Higher-level systematics in amphibians is relatively stable. However, recent phylogenetic studies of African torrent-frogs have uncovered high divergence in these phenotypically and ecologically similar frogs, in particular between West African torrent-frogs versus Central (Petropedetes) and East African (Arthroleptides and Ericabatrachus) lineages. Because of the considerable molecular divergence, and external morphology of the single West African torrent-frog species a new genus was erected (Odontobatrachus). In this study we aim to clarify the systematic position of West African torrent-frogs (Odontobatrachus). We determine the relationships of torrent-frogs using a multi-locus, nuclear and mitochondrial, dataset and include genera of all African and Asian ranoid families. Using microtomographic scanning we examine osteology and external morphological features of West African torrent-frogs to compare them with other ranoids. Results Our analyses reveal Petropedetidae (Arthroleptides, Ericabatrachus, Petropedetes) as the sister taxon of the Pyxicephalidae. The phylogenetic position of Odontobatrachus is clearly outside Petropedetidae, and not closely related to any other ranoid family. According to our time-tree estimation Odontobatrachus has been separated from other frog lineages since the Cretaceous (90.1 Ma; confidence interval: 84.2-97.1 Ma). Along with this molecular evidence, osteological and external diagnostic characters recognize West African torrentfrogs as distinct from other ranoids and provide strong support for the necessity of the recognition of a new family of frogs. This is the only endemic vertebrate family occurring in the Upper Guinea biodiversity hotspot. Conclusion Based on molecular and morphological distinctiveness, the West African torrent-frog Odontobatrachus natator is allocated to a newly described anuran family. The discovery of an endemic vertebrate family in West Africa highlights the Upper Guinean forests as an outstanding, but highly endangered biodiversity hotspot. [ABSTRACT FROM AUTHOR]

ABSTRACT The axolotl is becoming one of the most used model organisms in developmental and regenerative studies but no publication has described in detail the development of its forelimb and hindlimb muscles. We describe and illustrate the ontogeny of these muscles in transgenic axolotls that express GFP in muscle fibers and discuss our results and data previously obtained by us and by other authors about limb regeneration in axolotls and ontogeny in frogs and other tetrapods. Our observations and comparisons: (1) demonstrate radio-ulnar and ventro-dorsal morphogenetic gradients in the order of axolotl forelimb muscle formation and differentiation, while in axolotl hindlimb ontogeny there are only proximo-distal and tibio-fibular gradients; some of the axolotl gradients are therefore different from the ulno-radial/fibulo-tibial fore- and hindlimb and the dorso-ventral hindimb ontogenetic morphogenetic gradients seen in frogs and amniotes such as chickens; (2) provide a potential explanation for the usual presence, in both limbs of taxa from all major tetrapod groups, of more radial/tibial muscles than ulnar/fibular muscles; (3) support the 'in-out' developmental mechanism of appendicular muscle formation; (4) offer new insights about the ancestral Bauplan of tetrapod limbs, including the striking similarity of the zeugopodial (forearm/leg) and autopodial (hand/foot) muscles of the two limbs and the ventro-dorsal symmetry of the zeugopodial muscles of a same limb; and (5) provide further evidence to corroborate the hypothesis that these similarities are due to derived homoplastic events that occurred during the fins-limbs transition and not due to forelimb-hindlimb serial homology. J. Exp. Zool. (Mol. Dev. Evol.) 322B: 106-127, 2014. © 2013 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

The discovery by Hans Spemann of the "organizer" tissue and its ability to induce the formation of the amphibian embryo's neural tube inspired leading embryologists to attempt to elucidate embryonic induction's underlying mechanisms. Since then several studies have described several developmental model system to better understand the role of specific signaling molecules, the interplay of different signals and tissue interactions in regulating tissue induction and patterning events. Different groups of workers set out to subject embryonic amphibian tissues and inductive adult organs to various extraction methods in the hope that the active agents could be isolated and chemically identified. in addition, a large number of well characterized chemical compounds were tested. [ABSTRACT FROM AUTHOR]

In order to establish patterns of phenotypic variability, 15 quantitative and 3 qualitative body traits of 74 populations grouped in 14 geographic areas from the Central part of the Balkan Peninsula were examined. Although results of our multivariate analysis indicate existence of significant differences among populations belonging to different geographical groups, clear patterns of variation have not been found. Reason for the absence of geographical structuring of morphological variation in the fire salamander could be due to palaeogeographic situation of the Balkan Peninsula during Pleistocene. [ABSTRACT FROM AUTHOR]