Pth reloaded: a new evolutionary perspective

The parathyroid hormone (PTH) family is a group of structurally-related secreted peptides involved in bone mineral homeostasis and multitude of developmental processes in vertebrates. These peptides mediate actions through PTH receptors (PTHRs), which belong to the transmembrane G protein-coupled receptor group. To date, genes encoding for PTH and PTHR have only been identified in chordates, suggesting that this signaling pathway may be an evolutionary innovation of our phylum. In vertebrates, we found up to six PTH and three PTHR different paralogs, varying in number between mammals and teleost fishes due to the different rounds of whole-genome duplication and specific gene losses suffered between the two groups of animals. The diversification of the PTH gene family has been accompanied by both functional divergence and convergence, making sometimes difficult the comparison between PTH peptides of teleosts and mammals. Here, we review the roles of all Pth peptides in fishes, and based on the evolutionary history of PTH paralogs, we propose a new and simple nomenclature from PTH1 to PTH4. Moreover, the recent characterization of the Pth4 in zebrafish allows us to consider the prominent role of the brain-to-bone signaling pathway in the regulation of bone development and homeostasis. Finally, comparison between PTH peptides of fish and mammals allows us to discuss an evolutionary model for PTH functions related to bone mineral balance during the vertebrate transition from an aquatic to a terrestrial environment

Loss-of-function mutations in the melanocortin 1 receptor cause disruption of dorso-ventral countershading in teleost fish

13 pages, 8 figuresThe melanocortin 1 receptor (MC1R) is the central melanocortin receptor involved in vertebrate pigmentation. Mutations in this gene cause variations in coat coloration in amniotes. Additionally, in mammals MC1R is the main receptor for agouti‐signaling protein (ASIP), making it the critical receptor for the establishment of dorsal‐ventral countershading. In fish, Mc1r is also involved in pigmentation, but it has been almost exclusively studied in relation to melanosome dispersion activity and as a putative genetic factor involved in dark/light adaptation. However, its role as the crucial component for the Asip1‐dependent control of dorsal‐ventral pigmentation remains unexplored. Using CRISPR/Cas9, we created mc1r homozygous knockout zebrafish and found that loss‐of‐function of mc1r causes a reduction of countershading and a general paling of the animals. We find ectopic development of melanophores and xanthophores, accompanied by a decrease in iridophore numbers in the ventral region of mc1r mutants. We also reveal subtle differences in the role of mc1r in repressing pigment cell development between the skin and scale niches in ventral regionsThis work was funded by the Spanish Economy and Competitiveness Ministry projects AGL2011‐23581, AGL2014‐52473R, AGL2017‐89648P to JR. Partial funding was obtained from AGL2016‐74857‐C3‐3‐R to JMCR. L. Cal was supported by predoctoral fellowship FPI funded by Spanish Economy and Competitiveness Ministry (AGL2011‐23581) and by predoctoral fellowship of the Spanish Personnel Research Training Program funded by Spanish Economy and Competitiveness Ministry (EEBB‐C‐14‐00467). P Suarez‐Bregua was supported by AGL2014‐52473R and AGL2017‐89648P project contractPeer reviewe

Environmental DNA (eDNA) for monitoring marine mammals: Challenges and opportunities

Monitoring marine mammal populations is essential to permit assessment of population status as required by both national and international legislation. Traditional monitoring methods often rely on visual and/or acoustic detections from vessels and aircraft, but limitations including cost, errors in the detection of some species and dependence on taxonomic expertise, as well as good weather and visibility conditions often limit the temporal and spatial scale of effective, long-term monitoring programs. In recent years, environmental DNA (eDNA) has emerged as a revolutionary tool for cost-effective, sensitive, noninvasive species monitoring in both terrestrial and aquatic realms. eDNA is a rapidly developing field and a growing number of studies have successfully implemented this approach for the detection and identification of marine mammals. Here, we review 21 studies published between 2012 and 2021 that employed eDNA for marine mammal monitoring including single species detection, biodiversity assessment and genetic characterization. eDNA has successfully been used to infer species presence (especially useful for rare, elusive or threatened species) and to characterize the population genetic structure, although additional research is needed to support the interpretation of non-detections. Finally, we discuss the challenges and the opportunities that eDNA could bring to marine mammal monitoring as a complementary tool to support visual and acoustic methods

Countershading in zebrafish results from an Asip1 controlled dorsoventral gradient of pigment cell differentiation.

13 pages, 8 figures.-- his article is licensed under a Creative Commons Attribution 4.0 International LicenseDorso-ventral (DV) countershading is a highly-conserved pigmentary adaptation in vertebrates. In mammals, spatially regulated expression of agouti-signaling protein (ASIP) generates the difference in shading by driving a switch between the production of chemically-distinct melanins in melanocytes in dorsal and ventral regions. In contrast, fish countershading seemed to result from a patterned DV distribution of differently-coloured cell-types (chromatophores). Despite the cellular differences in the basis for counter-shading, previous observations suggested that Agouti signaling likely played a role in this patterning process in fish. To test the hypotheses that Agouti regulated counter-shading in fish, and that this depended upon spatial regulation of the numbers of each chromatophore type, we engineered asip1 homozygous knockout mutant zebrafish. We show that loss-of-function asip1 mutants lose DV countershading, and that this results from changed numbers of multiple pigment cell-types in the skin and on scales. Our findings identify asip1 as key in the establishment of DV countershading in fish, but show that the cellular mechanism for translating a conserved signaling gradient into a conserved pigmentary phenotype has been radically altered in the course of evolutionThis work was funded by the Spanish Economy and Competitiveness Ministry projects AGL2011-23581, AGL2014-52473R, AGL2017-89648P to JR, and by a BBSRC SWBio DTP Studentship to JO. Partial funding was obtained from AGL2016-74857-C3-3-R to JMCR. L. Cal was supported by pre-doctoral fellowship FPI funded by Spanish Economy and Competitiveness Ministry (AGL2011-23581) and by pre-doctoral fellowship of the Spanish Personnel Research Training Program funded by Spanish Economy and Competitiveness Ministry (EEBB-C-14- 00467). P Suarez-Bregua was supported by a Campus do Mar PhD grant, Xunta de Galicia and AGL2014-52473R project contract.Peer reviewe

Pth4, an ancient parathyroid hormone lost in eutherian mammals, reveals a new brain-to-bone signaling pathway

Regulation of bone development, growth, and remodeling traditionally has been thought to depend on endocrine and autocrine/paracrine modulators. Recently, however, brain-derived signals have emerged as key regulators of bone metabolism, although their mechanisms of action have been poorly understood. We reveal the existence of an ancient parathyroid hormone (Pth)4 in zebrafish that was secondarily lost in the eutherian mammals' lineage, including humans, and that is specifically expressed in neurons of the hypothalamus and appears to be a central neural regulator of bone development and mineral homeostasis. Transgenic fish lines enabled mapping of axonal projections leading from the hypothalamus to the brainstem and spinal cord. Targeted laser ablation demonstrated an essential role for of pth4-expressing neurons in larval bone mineralization. Moreover, we show that Runx2 is a direct regulator of pth4 expression and that Pth4 can activate cAMP signaling mediated by Pth receptors. Finally, gain-of-function experiments show that Pth4 can alter calcium/phosphorus levels and affect expression of genes involved in phosphate homeostasis. Based on our discovery and characterization of Pth4, we propose a model for evolution of bone homeostasis in the context of the vertebrate transition from an aquatic to a terrestrial lifestyle.Spanish Economy and Competitiveness Ministry Project [ALG2011-23581, AGL2014-52473R]; Portuguese Foundation for Science and Technology [PTDC/BIA-ANM/4225/2012-phos-fate]; U. S. National Institutes of Health/Office of the Director Grant [R01OD011116, R01 RR020833]; Generalitat de Catalunya [SGR2014-290]; Spanish Economy and Competitiveness Ministry [BFU2010-14875]; Science and Innovation Ministry [AGL2010-22247-C03-01]; Campus do Mar Ph.D. grant; Xunta de Galicia (Santiago, Spain) [AGL2014-52473R]info:eu-repo/semantics/publishedVersio

Regulación neural da homeostase mineral do óso : novas perspectivas de peixes

Diseases and malformations are ones of the major hurdles for the developing aquaculture industry. Thus, despite the improved methodologies for farming of marine and fresh water fish species, egg and larval viability in some species is still very low as a consequence of a high incidence of dystrophies. Often skeletal pathologies may be a combination of several deformities, however, neck, vertebral, and spinal disorders are most prevalent. Many times the dystrophies are not immediately apparent (or detected) leading to wasteful use of food, energy, space and human resources until dystrophic fish are graded and removed. Previous studies suggest that malformations are induced in early stages during the embryonic and larval periods of life, although the causes and mechanisms responsible are not well understood. It has been proposed that alteration of skeletal development is probably a result of complex interactions between genetic, nutritional and environmental factors. Currently, there is scanty information about the development and metabolism of bone in fish species. Specifically, we will focus on Pth4 (PTHL, parathyroid hormone like), a discovered member of PTH family of peptides that are known to play critical roles in phosphate and calcium homeostasis and bone development in human and other vertebrates. Most studies have tried to provide insights about peptide-receptor interaction for several ligands from the PTH family to understand and treat disorders of bone and mineral metabolism. Pth4 (PTHL) gene was identified and isolated for the first time in the teleost Takifugu rubripes and then in other vertebrates like Xenopus and chicken, with the exception of placental mammals. We aim to characterize the function of Pth4 (PTHL) and its genetic regulation as a possible gene involved on the skeletal development in zebrafish.Las enfermedades y malformaciones son dos de los principales obstáculos para el desarrollo de la industria acuícola. Así, a pesar de las mejoras introducidas en el cultivo de peces de agua marina y dulce, la viabilidad de huevos y larvas es todavía baja en algunas especies como consecuencia de la alta incidencia de distrofias. Normalmente las patologías esqueléticas son una combinación de varias deformidades, sin embargo los trastornos de cuello, vértebras y de columna son los más frecuentes. La mayoría de las veces las distrofias no son inmediatamente aparentes (o detectadas) lo cual conduce a la pérdida de alimentos, energía, espacio y recursos humanos hasta que los peces malformados son clasificados y eliminados. Estudios previos sugieren que las malformaciones son inducidas en las primeras etapas durante los períodos embrionario y larval, aunque no se conocen bien las causas y los mecanismos responsables. Se ha propuesto que la alteración del desarrollo esquelético es probablemente un resultado de complejas interacciones entre factores genéticos, ambientales y nutricionales. Actualmente, hay escasez de información sobre el desarrollo y el metabolismo de hueso en especies de peces . En concreto, nos centraremos en la Pth4 (PTHL, parathyroid hormone like), un miembro de la familia de las hormonas paratiroideas que juegan un papel crítico en la homeostasis del fosfato y del calcio y el desarrollo esquelético en humanos y otros vertebrados. La mayoría de los estudios han tratado de proporcionar información acerca de la interacción péptido-receptor para varios ligandos de la familia de PTH para entender los trastornos del metabolismo óseo y mineral. El gen Pth4 (PTHL) fue identificado por primera vez en el teleósteo Takifugu rubripes y luego en otros vertebrados como en Xenopus y Gallus, con la excepción de los mamíferos placentarios. Nuestro objetivo es caracterizar la función de Pth4 (PTHL) y su regulación genética como un posible gen implicado en el desarrollo esquelético en el pez cebra.As enfermidades e malformacións son dous dos principais obstáculos para o desenvolvemento da industria acuícola. Así, a pesar das melloras introducidas no cultivo de peixes de auga mariña e doce, a viabilidade de ovos e larvas é aínda baixa nalgunhas especies como consecuencia da alta incidencia de distrofias. Normalmente as patoloxías esqueléticas son unha combinación de varias deformidades, non obstante os trastornos de colo, vértebras e de columna son os máis frecuentes. A maioría das veces as distrofias non son inmediatamente aparentes (ou detectadas) o cal conduce á perda de alimentos, enerxía, espazo e recursos humanos ata que os peixes malformados son clasificados e eliminados. Estudos previos suxiren que as malformacións son inducidas nas primeiras etapas durante os períodos embrionario e larval, aínda que non se coñecen ben as causas e os mecanismos responsables. Propúxose que a alteración do desenvolvemento esquelético é probablemente un resultado de complexas interaccións entre factores xenéticos, ambientais e nutricionais. Actualmente, hai escaseza de información sobre o desenvolvemento e o metabolismo de óso en especies de peixes. En concreto, centrarémonos na Pth4 (PTHL, parathyroid hormone like), un membro da familia das hormonas paratiroideas que xogan un papel crítico na homeostase do fosfato e do calcio e o desenvolvemento esquelético en humanos e outros vertebrados. A maioría dos estudos trataron de proporcionar información acerca da interacción péptido-receptor para varios ligandos da familia de PTH para entender os trastornos do metabolismo óseo e mineral. O xene Pth4 (PTHL) foi identificado por primeira vez no teleósteo Takifugu rubripes e logo noutros vertebrados como en Xenopus e Gallus, coa excepción dos mamíferos placentarios. O noso obxectivo é caracterizar a función de Pth4 (PTHL) e a súa regulación xenética como un posible xene implicado no desenvolvemento esquelético no peixe cebra.Ministerio de Economía y Competitividad de EspañaXunta de Galici

Characterization of a new fish-derived bioactive neuropeptide involved in bone remodelling. Its physiological function and therapeutic potential.

A complex network of autocrine and paracrine signals, hormones and neuronal factors preserve the structural integrity of the skeleton and regulate mineral metabolism in vertebrates. We have characterized a new neuropeptide belonging to parathyroid hormone (PTH) family. PTH family members are known to play a key role in maintaining mineral homeostasis, bone remodeling and in regulating embryonic development of skeleton and other tissues. This new neuropeptide is synthesized by two clusters of neurons located in lateral hypothalamus as showed in whole mount in situ hybridization. The functional characterization of the gene using a stable transgenic line revealed its key role in the regulation of bone mineral density. Moreover, phylogenetic analyses and comparative genomics results of conserved synteny reveal that this new neuropeptide is a new ohnolog of the PTH family present in teleosts and some tetrapods like chicken, but absent in mammals . Our findings suggest a new brain to bone pathway, where neuronal factors from hypothalamus signal to receptors on bone cells promoting bone remodeling. Further investigations about this new neuropeptide system would be relevant for developing therapies for bone mineral disorders in humans, since this neuropeptide has a conserved domain similar to other PTH-related peptides which have anabolic effects on bone

PTH Reloaded: A New Evolutionary Perspective

The parathyroid hormone (PTH) family is a group of structurally-related secreted peptides involved in bone mineral homeostasis and multitude of developmental processes in vertebrates. These peptides mediate actions through PTH receptors (PTHRs), which belong to the transmembrane G protein-coupled receptor group. To date, genes encoding for PTH and PTHR have only been identified in chordates, suggesting that this signaling pathway may be an evolutionary innovation of our phylum. In vertebrates, we found up to six PTH and three PTHR different paralogs, varying in number between mammals and teleost fishes due to the different rounds of whole-genome duplication and specific gene losses suffered between the two groups of animals. The diversification of the PTH gene family has been accompanied by both functional divergence and convergence, making sometimes difficult the comparison between PTH peptides of teleosts and mammals. Here, we review the roles of all Pth peptides in fishes, and based on the evolutionary history of PTH paralogs, we propose a new and simple nomenclature from PTH1 to PTH4. Moreover, the recent characterization of the Pth4 in zebrafish allows us to consider the prominent role of the brain-to-bone signaling pathway in the regulation of bone development and homeostasis. Finally, comparison between PTH peptides of fish and mammals allows us to discuss an evolutionary model for PTH functions related to bone mineral balance during the vertebrate transition from an aquatic to a terrestrial environment

Unmanned Aerial Vehicles (UAVs) in Marine Mammal Research: A Review of Current Applications and Challenges

Research on the ecology and biology of marine mammal populations is necessary to understand ecosystem dynamics and to support conservation management. Emerging monitoring tools and instruments offer the opportunity to obtain such information in an affordable and effective way. In recent years, unmanned aerial vehicles (UAVs) have become an important tool in the study of marine mammals. Here, we reviewed 169 research articles using UAVs to study marine mammals, published up until December 2022. The goals of these studies included estimating the number of individuals in populations and groups via photo-identification, determining biometrics and body condition through photogrammetry, collecting blow samples, and studying behavioural patterns. UAVs can be a valuable, non-invasive, and useful tool for a wide range of applications in marine mammal research. However, it is important to consider some limitations of this technology, mainly associated with autonomy, resistance to the marine environment, and data processing time, which could probably be overcome in the near future

Pth reloaded: a new evolutionary perspective

The parathyroid hormone (PTH) family is a group of structurally-related secreted peptides involved in bone mineral homeostasis and multitude of developmental processes in vertebrates. These peptides mediate actions through PTH receptors (PTHRs), which belong to the transmembrane G protein-coupled receptor group. To date, genes encoding for PTH and PTHR have only been identified in chordates, suggesting that this signaling pathway may be an evolutionary innovation of our phylum. In vertebrates, we found up to six PTH and three PTHR different paralogs, varying in number between mammals and teleost fishes due to the different rounds of whole-genome duplication and specific gene losses suffered between the two groups of animals. The diversification of the PTH gene family has been accompanied by both functional divergence and convergence, making sometimes difficult the comparison between PTH peptides of teleosts and mammals. Here, we review the roles of all Pth peptides in fishes, and based on the evolutionary history of PTH paralogs, we propose a new and simple nomenclature from PTH1 to PTH4. Moreover, the recent characterization of the Pth4 in zebrafish allows us to consider the prominent role of the brain-to-bone signaling pathway in the regulation of bone development and homeostasis. Finally, comparison between PTH peptides of fish and mammals allows us to discuss an evolutionary model for PTH functions related to bone mineral balance during the vertebrate transition from an aquatic to a terrestrial environment