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Robert D. Miller - One of the best experts on this subject based on the ideXlab platform.
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developmental and comparative immunology single cell transcriptome analysis of the b cell repertoire reveals the usage of immunoglobulins in the gray short tailed Opossum monodelphis domestica
Developmental and Comparative Immunology, 2021Co-Authors: Andrea L Schraven, Robert D. Miller, Victoria L. Hansen, Kimberly A Morrissey, Hayley J Stannard, Oselyne Tw Ong, Daniel C Douek, Julie M OldAbstract:B-cells are key to humoral immunity, are found in multiple lymphoid organs, and have the unique ability to mediate the production of antigen-specific antibodies in the presence of pathogens. The marsupial immunoglobulin (Ig) heavy (H) chain locus encodes four constant region isotypes, IgA, IgG, IgM and IgE, but no IgD, and there are two light (L) chain isotypes, lambda (Igλ) and kappa (Igκ). To gain an understanding of the marsupial humoral immune system, B-cell transcriptomes generated by single-cell RNA sequencing from gray Short-Tailed Opossum (Monodelphis domestica) splenocytes, and peripheral blood mononuclear cells were analysed. The cells used were from a single unimmunized animal and the majority of B-cells were transcribing IgM heavy chains. The ratio of Ig light chain use was roughly 2:1, Igλ:Igκ in this individual. This was not predicted due to Igκ being the more complex of the two L chain loci. The variable (V) gene segment pairs used in individual B-cells confirm greater diversity provided by the L chain V. This study is the first to report on using single cell analysis to investigate Ig repertoires in a marsupial and confirms a number of prior hypothesis, as well as revealing some surprises.
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On the prenatal initiation of T cell development in the Opossum Monodelphis domestica.
Journal of Anatomy, 2017Co-Authors: Victoria L. Hansen, Robert D. MillerAbstract:Thymus-dependent lymphocytes (T cells) are a critical cell lineage in the adaptive immune system of all jawed vertebrates. In eutherian mammals the initiation of T cell development takes place prenatally and the offspring of many species are born relatively immuno-competent. Marsupials, in contrast, are born in a comparatively altricial state and with a less well developed immune system. As such, marsupials are valuable models for studying the peri- and postnatal initiation of immune system development in mammals. Previous results supported a lack of prenatal T cell development in a variety of marsupial species. In the gray Short-Tailed Opossum, Monodelphis domestica, however, there was evidence that αβT cells were present on postnatal day 1 and likely initiated development prenatally. Demonstrated here is the presence of CD3e+ lymphocytes in late-stage embryos at a site in the upper thoracic cavity, the site of an early developing thymus. CD3e+ cells were evident as early as 48 h prior to parturition. In day 14 embryos, where there is clear organogenesis, CD3e+ cells were only found at the site of the early thymus, consistent with no extra-thymic sites of T cell development in the Opossum. These observations are the first evidence of prenatal T cell lineage commitment in any marsupial.
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transcriptomic changes associated with pregnancy in a marsupial the gray short tailed Opossum monodelphis domestica
PLOS ONE, 2016Co-Authors: Victoria L. Hansen, Faye D Schilkey, Robert D. MillerAbstract:Live birth has emerged as a reproductive strategy many times across vertebrate evolution; however, mammals account for the majority of viviparous vertebrates. Marsupials are a mammalian lineage that last shared a common ancestor with eutherians (placental mammals) over 148 million years ago. Marsupials are noted for giving birth to highly altricial young after a short gestation, and represent humans’ most distant viviparous mammalian relatives. Here we ask what insight can be gained into the evolution of viviparity in mammals specifically and vertebrates in general by analyzing the global uterine transcriptome in a marsupial. Transcriptome analyses were performed using NextGen sequencing of uterine RNA samples from the gray Short-Tailed Opossum, Monodelphis domestica. Samples were collected from late stage pregnant, virgin, and non-pregnant experienced breeders. Three different algorithms were used to determine differential expression, and results were confirmed by quantitative PCR. Over 900 Opossum gene transcripts were found to be significantly more abundant in the pregnant uterus than non-pregnant, and over 1400 less so. Most with increased abundance were genes related to metabolism, immune systems processes, and transport. This is the first study to characterize the transcriptomic differences between pregnant, non-pregnant breeders, and virgin marsupial uteruses and helps to establish a set of pregnancy-associated genes in the Opossum. These observations allowed for comparative analyses of the differentially transcribed genes with other mammalian and non-mammalian viviparous species, revealing similarities in pregnancy related gene expression over 300 million years of amniote evolution.
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A VpreB3 homologue in a marsupial, the gray Short-Tailed Opossum, Monodelphis domestica
Immunogenetics, 2012Co-Authors: Xinxin Wang, Zuly E. Parra, Robert D. MillerAbstract:A VpreB surrogate light (SL) chain was identified for the first time in a marsupial, the Opossum Monodelphis domestica . Comparing the Opossum VpreB to homologues from eutherian (placental mammals) and avian species supported the marsupial gene being VpreB3 . VpreB3 is a protein that is not known to traffic to the cell surface as part of the pre-B cell receptor. Rather, VpreB3 associates with nascent immunoglobulin chains in the endoplasmic reticulum. Homologues of other known SL chains VpreB1 , VpreB2 , and λ5 , which are found in eutherian mammals, were not found in the Opossum genome, nor have they been identified in the genomes of nonmammals. VpreB3 likely evolved from earlier gene duplication, independent of that which generated VpreB1 and VpreB2 in eutherians. The apparent absence of VpreB1, VpreB2, and λ5 in marsupials suggests that an extracellular pre-B cell receptor containing SL chains, as it has been defined in humans and mice, may be unique to eutherian mammals. In contrast, the conservation of VpreB3 in marsupials and its presence in nonmammals is consistent with previous hypotheses that it is playing a more primordial role in B cell development.
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On the genomics of immunoglobulins in the gray, Short-Tailed Opossum Monodelphis domestica
Immunogenetics, 2009Co-Authors: Xinxin Wang, Robert D. MillerAbstract:Annotated maps of the IGH , IGK , and IGL loci in the gray, Short-Tailed Opossum Monodelphis domestica were generated from analyses of the available whole genome sequence for this species. Analyses of their content and organization confirmed a number of previous conclusions based on characterization of complementary DNAs encoding Opossum immunoglobulin heavy and light chains and limited genomic analysis, including (a) the predominance of a single immunoglobulin heavy chain variable region (IGHV) subgroup and clan, (b) the presence of a single immunoglobulin (Ig)G subclass, (c) the apparent absence of an IgD, and (d) the general organization and V gene complexity of the IGK and IGL light chain loci. In addition, several unexpected discoveries were made including the presence of a partial V to D, germline-joined IGHV segment, the first germline-joined Ig V gene to be found in a mammal. In addition was the presence of a larger number of IGKV subgroups than had been previously identified. With this report, annotated maps of the major histocompatibility complex, T-cell receptor, and immunoglobulin loci have been completed for M. domestica , the only non-eutherian mammalian species for which this has been accomplished, strengthening the utility of this species as a model organism.
Kevin R. Nicholas - One of the best experts on this subject based on the ideXlab platform.
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gene expression profiling of postnatal lung development in the marsupial gray short tailed Opossum monodelphis domestica highlights conserved developmental pathways and specific characteristics during lung organogenesis
BMC Genomics, 2018Co-Authors: Vengamanaidu Modepalli, Kevin R. Nicholas, Amit Kumar, Julie A Sharp, Norman R Saunders, Christophe LefevreAbstract:After a short gestation, marsupials give birth to immature neonates with lungs that are not fully developed and in early life the neonate partially relies on gas exchange through the skin. Therefore, significant lung development occurs after birth in marsupials in contrast to eutherian mammals such as humans and mice where lung development occurs predominantly in the embryo. To explore the mechanisms of marsupial lung development in comparison to eutherians, morphological and gene expression analysis were conducted in the gray Short-Tailed Opossum (Monodelphis domestica). Postnatal lung development of Monodelphis involves three key stages of development: (i) transition from late canalicular to early saccular stages, (ii) saccular and (iii) alveolar stages, similar to developmental stages overlapping the embryonic and perinatal period in eutherians. Differentially expressed genes were identified and correlated with developmental stages. Functional categories included growth factors, extracellular matrix protein (ECMs), transcriptional factors and signalling pathways related to branching morphogenesis, alveologenesis and vascularisation. Comparison with published data on mice highlighted the conserved importance of extracellular matrix remodelling and signalling pathways such as Wnt, Notch, IGF, TGFβ, retinoic acid and angiopoietin. The comparison also revealed changes in the mammalian gene expression program associated with the initiation of alveologenesis and birth, pointing to subtle differences between the non-functional embryonic lung of the eutherian mouse and the partially functional developing lung of the marsupial Monodelphis neonates. The data also highlighted a subset of contractile proteins specifically expressed in Monodelphis during and after alveologenesis. The results provide insights into marsupial lung development and support the potential of the marsupial model of postnatal development towards better understanding of the evolution of the mammalian bronchioalveolar lung.
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Gene expression profiling of postnatal lung development in the marsupial gray Short-Tailed Opossum (Monodelphis domestica) highlights conserved developmental pathways and specific characteristics during lung organogenesis
BMC, 2018Co-Authors: Vengamanaidu Modepalli, Kevin R. Nicholas, Amit Kumar, Julie A Sharp, Norman R Saunders, Christophe LefevreAbstract:Abstract Background After a short gestation, marsupials give birth to immature neonates with lungs that are not fully developed and in early life the neonate partially relies on gas exchange through the skin. Therefore, significant lung development occurs after birth in marsupials in contrast to eutherian mammals such as humans and mice where lung development occurs predominantly in the embryo. To explore the mechanisms of marsupial lung development in comparison to eutherians, morphological and gene expression analysis were conducted in the gray Short-Tailed Opossum (Monodelphis domestica). Results Postnatal lung development of Monodelphis involves three key stages of development: (i) transition from late canalicular to early saccular stages, (ii) saccular and (iii) alveolar stages, similar to developmental stages overlapping the embryonic and perinatal period in eutherians. Differentially expressed genes were identified and correlated with developmental stages. Functional categories included growth factors, extracellular matrix protein (ECMs), transcriptional factors and signalling pathways related to branching morphogenesis, alveologenesis and vascularisation. Comparison with published data on mice highlighted the conserved importance of extracellular matrix remodelling and signalling pathways such as Wnt, Notch, IGF, TGFβ, retinoic acid and angiopoietin. The comparison also revealed changes in the mammalian gene expression program associated with the initiation of alveologenesis and birth, pointing to subtle differences between the non-functional embryonic lung of the eutherian mouse and the partially functional developing lung of the marsupial Monodelphis neonates. The data also highlighted a subset of contractile proteins specifically expressed in Monodelphis during and after alveologenesis. Conclusion The results provide insights into marsupial lung development and support the potential of the marsupial model of postnatal development towards better understanding of the evolution of the mammalian bronchioalveolar lung
Adele M. H. Seelke - One of the best experts on this subject based on the ideXlab platform.
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Evolution of mammalian sensorimotor cortex: Thalamic projections to parietal cortical areas in Monodelphis domestica
Frontiers Media S.A., 2015Co-Authors: James Clinton Dooley, Adele M. H. Seelke, Leah Krubitzer, Joao G. Franca, Dylan Francis CookeAbstract:The current experiments build upon previous studies designed to reveal the network of parietal cortical areas present in the common mammalian ancestor. Understanding this ancestral network is essential for highlighting the basic somatosensory circuitry present in all mammals, and how this basic plan was modified to generate species specific behaviors. Our animal model, the Short-Tailed Opossum (Monodelphis domestica), is a South American marsupial that has been proposed to have a similar ecological niche and morphology to the earliest common mammalian ancestor. In this investigation, we injected retrograde neuroanatomical tracers into the face and body representations of primary somatosensory cortex (S1), the rostral and caudal somatosensory fields (SR and SC), as well as a multimodal region (MM). Projections from different architectonically defined thalamic nuclei were then quantified. Our results provide further evidence to support the hypothesized basic mammalian plan of thalamic projections to S1, with the lateral and medial ventral posterior thalamic nuclei (VPl and VPm) projecting to S1 body and S1 face, respectively. Additional strong projections are from the medial division of posterior nucleus (Pom). SR receives projections from several midline nuclei, including the medial dorsal, ventral medial nucleus, and Pom. SC and MM show similar patterns of connectivity, with projections from the ventral anterior and ventral lateral nuclei, VPm and VPl, and the entire posterior nucleus (medial and lateral). Notably, MM is distinguished from SC by relatively dense projections from the dorsal division of the lateral geniculate nucleus and pulvinar. We discuss the finding that S1 of the Short-Tailed Opossum has a similar pattern of projections as other marsupials and mammals, but also some distinct projections not present in other mammals. Further we provide additional support for a primitive posterior parietal cortex which receives input from multiple modalities
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photic preference of the short tailed Opossum monodelphis domestica
Neuroscience, 2014Co-Authors: Adele M. H. Seelke, James C. Dooley, Leah KrubitzerAbstract:The gray Short-Tailed Opossum (Monodelphis domestica) is a nocturnal South American marsupial that has been gaining popularity as a laboratory animal. How- ever, compared to traditional laboratory animals like rats, very little is known about its behavior, either in the wild or in a laboratory setting. Here we investigated the photic pref- erence of the Short-Tailed Opossum. Opossums were placed in a circular testing arena and allowed to move freely between dark (0 lux) and light (1.4, 40, or 400 lux) sides of the arena. In each of these conditions Opossums spent significantly more time in the dark than in the illuminated side and a greater proportion of time in the dark than would be expected by chance. In the high-contrast (400 lux) illu- mination condition, the mean bout length (i.e., duration of one trip on the light or dark side) was significantly longer on the dark side than on the light side. When we examined the number of bouts greater than 30 and 60 s in duration, we found a significant difference between the light and dark sides in all light contrast conditions. These data indicate that the Short-Tailed Opossum prefers the dark to the light, and can also detect very slight differences in light intensity. We conclude that although rats and Opossums share many similar characteristics, including ecological niche, their divergent evolutionary heritage results in vastly different behavioral capabilities. Only by observing the behavioral capabilities and preferences of Opossums will we be able to manipulate the experimental environment to best elicit and elucidate their behavior and alterations in behavior that can arise from experimental manipulations. 2014 IBRO. Published by Elsevier Ltd. All rights reserved.
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Photic preference of the Short-Tailed Opossum (Monodelphis domestica)
Neuroscience, 2014Co-Authors: Adele M. H. Seelke, James C. Dooley, Leah KrubitzerAbstract:The gray Short-Tailed Opossum (Monodelphis domestica) is a nocturnal South American marsupial that has been gaining popularity as a laboratory animal. However, compared to traditional laboratory animals like rats, very little is known about its behavior, either in the wild or in a laboratory setting. Here we investigated the photic preference of the Short-Tailed Opossum. Opossums were placed in a circular testing arena and allowed to move freely between dark (0 lux) and light (∼1.4, 40, or 400 lux) sides of the arena. In each of these conditions Opossums spent significantly more time in the dark than in the illuminated side and a greater proportion of time in the dark than would be expected by chance. In the high-contrast (∼400 lux) illumination condition, the mean bout length (i.e., duration of one trip on the light or dark side) was significantly longer on the dark side than on the light side. When we examined the number of bouts greater than 30 and 60s in duration, we found a significant difference between the light and dark sides in all light contrast conditions. These data indicate that the Short-Tailed Opossum prefers the dark to the light, and can also detect very slight differences in light intensity. We conclude that although rats and Opossums share many similar characteristics, including ecological niche, their divergent evolutionary heritage results in vastly different behavioral capabilities. Only by observing the behavioral capabilities and preferences of Opossums will we be able to manipulate the experimental environment to best elicit and elucidate their behavior and alterations in behavior that can arise from experimental manipulations.
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Visual acuity in the Short-Tailed Opossum (Monodelphis domestica).
Neuroscience, 2012Co-Authors: James C. Dooley, Hoang Nguyen, Adele M. H. SeelkeAbstract:Monodelphis domestica (Short-Tailed Opossum) is an emerging animal model for studies of neural development due to the extremely immature state of the nervous system at birth and its subsequent rapid growth to adulthood. Yet little is known about its normal sensory discrimination abilities. In the present investigation, visual acuity was determined in this species using the optokinetic test (OPT), which relies on involuntary head tracking of a moving stimulus and can be easily elicited using a rotating visual stimulus of varying spatial frequencies. Using this methodology, we determined that the acuity of Monodelphis is 0.58 cycles per degree (cpd), which is similar to the acuity of rats using the same methodology, and higher than in mice. However, acuity in the Short-Tailed Opossum is lower than in other marsupials. This is in part due to the methodology used to determine acuity, but may also be due to differences in diel patterns, lifestyle and phylogeny. We demonstrate that for the Short-Tailed Opossum, the OPT is a rapid and reliable method of determining a baseline acuity and can be used to study enhanced acuities due to cortical plasticity.
Leah Krubitzer - One of the best experts on this subject based on the ideXlab platform.
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performance and behavioral flexibility on a complex motor task depend on available sensory inputs in early blind and sighted short tailed Opossums
bioRxiv, 2020Co-Authors: Mackenzie Englund, Samaan Faridjoo, Chris Iyer, Leah KrubitzerAbstract:The early loss of vision results in a reorganized visual cortex that processes tactile and auditory inputs. Recent studies in the Short-Tailed Opossum (Monodelphis domestica) found that the connections and response properties of neurons in somatosensory cortex of early blind animals are also altered. While research in humans and other mammals shows that early vision loss leads to heightened abilities on discrimination tasks involving the spared senses, if and how this superior discrimination leads to adaptive sensorimotor behavior has yet to be determined. Moreover, little is known about the extent to which blind animals rely on the spared senses. Here, we tested early blind Opossums on a sensorimotor task involving somatosensation and found that they had increased limb placement accuracy. However, increased reliance on tactile inputs in early blind animals resulted in greater deficits in limb placement and behavioral flexibility when the whiskers were trimmed.
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the evolution of whisker mediated somatosensation in mammals sensory processing in barrelless s1 cortex of a marsupial monodelphis domestica
The Journal of Comparative Neurology, 2016Co-Authors: Deepa L Ramamurthy, Leah KrubitzerAbstract:Movable tactile sensors in the form of whiskers are present in most mammals, but sensory coding in the cortical whisker representation has been studied almost exclusively in mice and rats. Many species that possess whiskers lack the modular "barrel" organization found in the primary somatosensory cortex (S1) of mice and rats, but it is unclear how whisker-related input is represented in these species. We used single-unit extracellular recording techniques to characterize receptive fields and response properties in S1 of Monodelphis domestica (Short-Tailed Opossum), a nocturnal, terrestrial marsupial that shared its last common ancestor with placental mammals over 160 million years ago. Short-Tailed Opossums lack barrels and septa in S1 but show active whisking behavior similar to that of mice and rats. Most neurons in Short-Tailed Opossum S1 exhibited multiwhisker receptive fields, including a single best whisker (BW) and lower magnitude responses to the deflection of surrounding whiskers. Mean tuning width was similar to that reported for mice and rats. Both symmetrical and asymmetrical receptive fields were present. Neurons tuned to ventral whiskers tended to show broad tuning along the rostrocaudal axis. Thus, despite the absence of barrels, most receptive field properties were similar to those reported for mice and rats. However, unlike those species, S1 neuronal responses to BW and surround whisker deflection showed comparable latencies in Short-Tailed Opossums. This dissimilarity suggests that some aspects of barrel cortex function may not generalize to tactile processing across mammalian species and may be related to differences in the architecture of the whisker-to-cortex pathway. J. Comp. Neurol. 524:3587-3613, 2016. © 2016 Wiley Periodicals, Inc.
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Evolution of mammalian sensorimotor cortex: Thalamic projections to parietal cortical areas in Monodelphis domestica
Frontiers Media S.A., 2015Co-Authors: James Clinton Dooley, Adele M. H. Seelke, Leah Krubitzer, Joao G. Franca, Dylan Francis CookeAbstract:The current experiments build upon previous studies designed to reveal the network of parietal cortical areas present in the common mammalian ancestor. Understanding this ancestral network is essential for highlighting the basic somatosensory circuitry present in all mammals, and how this basic plan was modified to generate species specific behaviors. Our animal model, the Short-Tailed Opossum (Monodelphis domestica), is a South American marsupial that has been proposed to have a similar ecological niche and morphology to the earliest common mammalian ancestor. In this investigation, we injected retrograde neuroanatomical tracers into the face and body representations of primary somatosensory cortex (S1), the rostral and caudal somatosensory fields (SR and SC), as well as a multimodal region (MM). Projections from different architectonically defined thalamic nuclei were then quantified. Our results provide further evidence to support the hypothesized basic mammalian plan of thalamic projections to S1, with the lateral and medial ventral posterior thalamic nuclei (VPl and VPm) projecting to S1 body and S1 face, respectively. Additional strong projections are from the medial division of posterior nucleus (Pom). SR receives projections from several midline nuclei, including the medial dorsal, ventral medial nucleus, and Pom. SC and MM show similar patterns of connectivity, with projections from the ventral anterior and ventral lateral nuclei, VPm and VPl, and the entire posterior nucleus (medial and lateral). Notably, MM is distinguished from SC by relatively dense projections from the dorsal division of the lateral geniculate nucleus and pulvinar. We discuss the finding that S1 of the Short-Tailed Opossum has a similar pattern of projections as other marsupials and mammals, but also some distinct projections not present in other mammals. Further we provide additional support for a primitive posterior parietal cortex which receives input from multiple modalities
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photic preference of the short tailed Opossum monodelphis domestica
Neuroscience, 2014Co-Authors: Adele M. H. Seelke, James C. Dooley, Leah KrubitzerAbstract:The gray Short-Tailed Opossum (Monodelphis domestica) is a nocturnal South American marsupial that has been gaining popularity as a laboratory animal. How- ever, compared to traditional laboratory animals like rats, very little is known about its behavior, either in the wild or in a laboratory setting. Here we investigated the photic pref- erence of the Short-Tailed Opossum. Opossums were placed in a circular testing arena and allowed to move freely between dark (0 lux) and light (1.4, 40, or 400 lux) sides of the arena. In each of these conditions Opossums spent significantly more time in the dark than in the illuminated side and a greater proportion of time in the dark than would be expected by chance. In the high-contrast (400 lux) illu- mination condition, the mean bout length (i.e., duration of one trip on the light or dark side) was significantly longer on the dark side than on the light side. When we examined the number of bouts greater than 30 and 60 s in duration, we found a significant difference between the light and dark sides in all light contrast conditions. These data indicate that the Short-Tailed Opossum prefers the dark to the light, and can also detect very slight differences in light intensity. We conclude that although rats and Opossums share many similar characteristics, including ecological niche, their divergent evolutionary heritage results in vastly different behavioral capabilities. Only by observing the behavioral capabilities and preferences of Opossums will we be able to manipulate the experimental environment to best elicit and elucidate their behavior and alterations in behavior that can arise from experimental manipulations. 2014 IBRO. Published by Elsevier Ltd. All rights reserved.
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Photic preference of the Short-Tailed Opossum (Monodelphis domestica)
Neuroscience, 2014Co-Authors: Adele M. H. Seelke, James C. Dooley, Leah KrubitzerAbstract:The gray Short-Tailed Opossum (Monodelphis domestica) is a nocturnal South American marsupial that has been gaining popularity as a laboratory animal. However, compared to traditional laboratory animals like rats, very little is known about its behavior, either in the wild or in a laboratory setting. Here we investigated the photic preference of the Short-Tailed Opossum. Opossums were placed in a circular testing arena and allowed to move freely between dark (0 lux) and light (∼1.4, 40, or 400 lux) sides of the arena. In each of these conditions Opossums spent significantly more time in the dark than in the illuminated side and a greater proportion of time in the dark than would be expected by chance. In the high-contrast (∼400 lux) illumination condition, the mean bout length (i.e., duration of one trip on the light or dark side) was significantly longer on the dark side than on the light side. When we examined the number of bouts greater than 30 and 60s in duration, we found a significant difference between the light and dark sides in all light contrast conditions. These data indicate that the Short-Tailed Opossum prefers the dark to the light, and can also detect very slight differences in light intensity. We conclude that although rats and Opossums share many similar characteristics, including ecological niche, their divergent evolutionary heritage results in vastly different behavioral capabilities. Only by observing the behavioral capabilities and preferences of Opossums will we be able to manipulate the experimental environment to best elicit and elucidate their behavior and alterations in behavior that can arise from experimental manipulations.
Christophe Lefevre - One of the best experts on this subject based on the ideXlab platform.
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gene expression profiling of postnatal lung development in the marsupial gray short tailed Opossum monodelphis domestica highlights conserved developmental pathways and specific characteristics during lung organogenesis
BMC Genomics, 2018Co-Authors: Vengamanaidu Modepalli, Kevin R. Nicholas, Amit Kumar, Julie A Sharp, Norman R Saunders, Christophe LefevreAbstract:After a short gestation, marsupials give birth to immature neonates with lungs that are not fully developed and in early life the neonate partially relies on gas exchange through the skin. Therefore, significant lung development occurs after birth in marsupials in contrast to eutherian mammals such as humans and mice where lung development occurs predominantly in the embryo. To explore the mechanisms of marsupial lung development in comparison to eutherians, morphological and gene expression analysis were conducted in the gray Short-Tailed Opossum (Monodelphis domestica). Postnatal lung development of Monodelphis involves three key stages of development: (i) transition from late canalicular to early saccular stages, (ii) saccular and (iii) alveolar stages, similar to developmental stages overlapping the embryonic and perinatal period in eutherians. Differentially expressed genes were identified and correlated with developmental stages. Functional categories included growth factors, extracellular matrix protein (ECMs), transcriptional factors and signalling pathways related to branching morphogenesis, alveologenesis and vascularisation. Comparison with published data on mice highlighted the conserved importance of extracellular matrix remodelling and signalling pathways such as Wnt, Notch, IGF, TGFβ, retinoic acid and angiopoietin. The comparison also revealed changes in the mammalian gene expression program associated with the initiation of alveologenesis and birth, pointing to subtle differences between the non-functional embryonic lung of the eutherian mouse and the partially functional developing lung of the marsupial Monodelphis neonates. The data also highlighted a subset of contractile proteins specifically expressed in Monodelphis during and after alveologenesis. The results provide insights into marsupial lung development and support the potential of the marsupial model of postnatal development towards better understanding of the evolution of the mammalian bronchioalveolar lung.
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Gene expression profiling of postnatal lung development in the marsupial gray Short-Tailed Opossum (Monodelphis domestica) highlights conserved developmental pathways and specific characteristics during lung organogenesis
BMC, 2018Co-Authors: Vengamanaidu Modepalli, Kevin R. Nicholas, Amit Kumar, Julie A Sharp, Norman R Saunders, Christophe LefevreAbstract:Abstract Background After a short gestation, marsupials give birth to immature neonates with lungs that are not fully developed and in early life the neonate partially relies on gas exchange through the skin. Therefore, significant lung development occurs after birth in marsupials in contrast to eutherian mammals such as humans and mice where lung development occurs predominantly in the embryo. To explore the mechanisms of marsupial lung development in comparison to eutherians, morphological and gene expression analysis were conducted in the gray Short-Tailed Opossum (Monodelphis domestica). Results Postnatal lung development of Monodelphis involves three key stages of development: (i) transition from late canalicular to early saccular stages, (ii) saccular and (iii) alveolar stages, similar to developmental stages overlapping the embryonic and perinatal period in eutherians. Differentially expressed genes were identified and correlated with developmental stages. Functional categories included growth factors, extracellular matrix protein (ECMs), transcriptional factors and signalling pathways related to branching morphogenesis, alveologenesis and vascularisation. Comparison with published data on mice highlighted the conserved importance of extracellular matrix remodelling and signalling pathways such as Wnt, Notch, IGF, TGFβ, retinoic acid and angiopoietin. The comparison also revealed changes in the mammalian gene expression program associated with the initiation of alveologenesis and birth, pointing to subtle differences between the non-functional embryonic lung of the eutherian mouse and the partially functional developing lung of the marsupial Monodelphis neonates. The data also highlighted a subset of contractile proteins specifically expressed in Monodelphis during and after alveologenesis. Conclusion The results provide insights into marsupial lung development and support the potential of the marsupial model of postnatal development towards better understanding of the evolution of the mammalian bronchioalveolar lung
