Marilyn Renfree | University of Melbourne (original) (raw)

Papers by Marilyn Renfree

Research paper thumbnail of Insulin is imprinted in the placenta of the marsupial, Macropus eugenii

Developmental Biology, 2007

Research paper thumbnail of Characterisation of marsupial PHLDA2 reveals eutherian specific acquisition of imprinting

BMC Evolutionary Biology, 2011

Research paper thumbnail of Genomic structure of tammar IGF2 including 3 TSS and comparison with mouse, human and opossum genomes

<p>Opossum (clone XX-223O16 ch5∶102112-82113), human (ch11∶2156597-2176597) and mouse (ch7∶... more <p>Opossum (clone XX-223O16 ch5∶102112-82113), human (ch11∶2156597-2176597) and mouse (ch7∶149841559-149861559), <i>IGF2</i> base genomes were aligned to tammar <i>IGF2</i> (clone MEKBa-346C2∶62540-82539). VISTA pairwise alignments using a 100 bp sliding window was performed between each species and tammar. Pink peaks represent areas of conservation of 70% over a minimum of 100 bp between tammar and opossum and 55% over a minimum of 50 bp between tammar and human or mouse. A dotted line indicates a region with 70% conservation between P1 and P2 in both marsupials and eutherians. A schematic of each <i>IGF2</i> gene is located above the VISTA plot to show relative location of the non-coding exons (open box), including the non-coding exons transcribed with the P0 TSS <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0041690#pone.0041690-Monk1&quot; target="_blank">[12]</a>, and coding exons (black box). Location of CpG sites are represented by vertical black bars below the VISTA plot.</p

Research paper thumbnail of Placental imprinting of SLC22A3 in the IGF2R imprinted domain is conserved in therian mammals

Epigenetics & Chromatin

Background The eutherian IGF2R imprinted domain is regulated by an antisense long non-coding RNA,... more Background The eutherian IGF2R imprinted domain is regulated by an antisense long non-coding RNA, Airn, which is expressed from a differentially methylated region (DMR) in mice. Airn silences two neighbouring genes, Solute carrier family 22 member 2 (Slc22a2) and Slc22a3, to establish the Igf2r imprinted domain in the mouse placenta. Marsupials also have an antisense non-coding RNA, ALID, expressed from a DMR, although the exact function of ALID is currently unknown. The eutherian IGF2R DMR is located in intron 2, while the marsupial IGF2R DMR is located in intron 12, but it is not yet known whether the adjacent genes SLC22A2 and/or SLC22A3 are also imprinted in the marsupial lineage. In this study, the imprinting status of marsupial SLC22A2 and SLC22A3 in the IGF2R imprinted domain in the chorio-vitelline placenta was examined in a marsupial, the tammar wallaby. Results In the tammar placenta, SLC22A3 but not SLC22A2 was imprinted. Tammar SLC22A3 imprinting was evident in placental...

Research paper thumbnail of Reproductive physiology of marsupials: References

Research paper thumbnail of Molecular conservation of marsupial and eutherian placentation and lactation

eLife, 2017

Eutherians are often mistakenly termed ‘placental mammals’, but marsupials also have a placenta t... more Eutherians are often mistakenly termed ‘placental mammals’, but marsupials also have a placenta to mediate early embryonic development. Lactation is necessary for both infant and fetal development in eutherians and marsupials, although marsupials have a far more complex milk repertoire that facilitates morphogenesis of developmentally immature young. In this study, we demonstrate that the anatomically simple tammar placenta expresses a dynamic molecular program that is reminiscent of eutherian placentation, including both fetal and maternal signals. Further, we provide evidence that genes facilitating fetal development and nutrient transport display convergent co-option by placental and mammary gland cell types to optimize offspring success.

Research paper thumbnail of Evolution of the Short Form of DNMT3A, DNMT3A2, Occurred in the Common Ancestor of Mammals

Genome Biology and Evolution

Genomic imprinting is found in marsupial and eutherian mammals, but not in monotremes. While the ... more Genomic imprinting is found in marsupial and eutherian mammals, but not in monotremes. While the primary regulator of genomic imprinting in eutherians is differential DNA methylation between parental alleles, conserved imprinted genes in marsupials tend to lack DNA methylation at their promoters. DNA methylation at eutherian imprinted genes is mainly catalyzed by a DNA methyltransferase (DNMT) enzyme, DNMT3A. There are two isoforms of eutherian DNMT3A: DNMT3A and DNMT3A2. DNMT3A2 is the primary isoform for establishing DNA methylation at eutherian imprinted genes and is essential for eutherian genomic imprinting. In this study, we investigated whether DNMT3A2 is also present in the two other mammalian lineages, marsupials and monotremes. We identified DNMT3A2 in both marsupials and monotremes, although imprinting has not been identified in monotremes. By analyzing genomic sequences and transcriptome data across vertebrates, we concluded that the evolution of DNMT3A2 occurred in the ...

Research paper thumbnail of Evolution of the Short Form of DNMT3A, DNMT3A2, Occurred in the Common Ancestor of Mammals

Genome Biology and Evolution

Genomic imprinting is found in marsupial and eutherian mammals, but not in monotremes. While the ... more Genomic imprinting is found in marsupial and eutherian mammals, but not in monotremes. While the primary regulator of genomic imprinting in eutherians is differential DNA methylation between parental alleles, conserved imprinted genes in marsupials tend to lack DNA methylation at their promoters. DNA methylation at eutherian imprinted genes is mainly catalyzed by a DNA methyltransferase (DNMT) enzyme, DNMT3A. There are two isoforms of eutherian DNMT3A: DNMT3A and DNMT3A2. DNMT3A2 is the primary isoform for establishing DNA methylation at eutherian imprinted genes and is essential for eutherian genomic imprinting. In this study, we investigated whether DNMT3A2 is also present in the two other mammalian lineages, marsupials and monotremes. We identified DNMT3A2 in both marsupials and monotremes, although imprinting has not been identified in monotremes. By analyzing genomic sequences and transcriptome data across vertebrates, we concluded that the evolution of DNMT3A2 occurred in the ...

Research paper thumbnail of Intensity of staining to IGF2 and IGF2R antibodies in the yolk sac trophoblast during the final third of gestation (A)

The intensity of staining was measured subjectively as described in the experimental procedures. ... more The intensity of staining was measured subjectively as described in the experimental procedures. The bilaminar (BYS) (shaded bars) and trilaminar yolk sac (TYS) (open bars) of matched samples were assessed independently. Samples were grouped into days 19–21 (n = 4), 22–24 (n = 5), and 25–26 (n = 4). Staining intensity to the IGF2 antibody was consistently stronger in the TYS, especially at days 25–26. Staining by the IGF2 antibody was notably lighter at days 19–21 than later stages (days 22 to 26). Staining by the IGF2R antibody did not differ notably between the bilaminar and trilaminar yolk sac, nor were there marked differences corresponding to developmental stage. Intensity of staining by IGF2 and IGF2R antibodies in yolk sac cells (B). Staining intensity was noticeably higher in the trophoblast (Tr) (stippled bars) than in the yolk sac endoderm (En) (striped bars) of the bilaminar (BYS) and trilaminar (TYS) for IGF2, but not IGF2R. The staining intensity represents the average ...

Research paper thumbnail of Intensity of staining to IGF2 and IGF2R antibodies in the yolk sac trophoblast during the final third of gestation (A)

The intensity of staining was measured subjectively as described in the experimental procedures. ... more The intensity of staining was measured subjectively as described in the experimental procedures. The bilaminar (BYS) (shaded bars) and trilaminar yolk sac (TYS) (open bars) of matched samples were assessed independently. Samples were grouped into days 19–21 (n = 4), 22–24 (n = 5), and 25–26 (n = 4). Staining intensity to the IGF2 antibody was consistently stronger in the TYS, especially at days 25–26. Staining by the IGF2 antibody was notably lighter at days 19–21 than later stages (days 22 to 26). Staining by the IGF2R antibody did not differ notably between the bilaminar and trilaminar yolk sac, nor were there marked differences corresponding to developmental stage. Intensity of staining by IGF2 and IGF2R antibodies in yolk sac cells (B). Staining intensity was noticeably higher in the trophoblast (Tr) (stippled bars) than in the yolk sac endoderm (En) (striped bars) of the bilaminar (BYS) and trilaminar (TYS) for IGF2, but not IGF2R. The staining intensity represents the average ...

Research paper thumbnail of A box plot showing the percent of total sequence masked by SINEs (dark blue), LINEs (light blue), LTR elements (purple), DNA elements (pink), simple repeats (teal), and low complexity regions (pale green) in intron 1, 1b, 9, 10, and 14 of (A)

The percent sequence coverage for each element over the entire region from is shown by open circl... more The percent sequence coverage for each element over the entire region from is shown by open circles. There was significantly less sequence masked by LTR and DNA elements in tammar compared to both mouse and human, while there was significantly more sequence occupied by low complexity regions (*). There was significantly less sequence occupied by LINEs in mouse compared to human (**). There was a large range in the sequence covered by LINEs in all species, but particularly in human and mouse. The percent sequence occupied by different types of repetitive elements in the region from , in all of , and in introns 9, 10, 1, 1b, and 14 assessed separately (B). The relative percentage of sequence occupied by LINEs is noticeably more than the percentage occupied by LINEs in any other intron from KCNQ1 and this increase was significant for mouse (*). No other significant differences in the relative amounts of sequence covered by different types of elements was seen between regions within spe...

Research paper thumbnail of A box plot showing the percent of total sequence masked by SINEs (dark blue), LINEs (light blue), LTR elements (purple), DNA elements (pink), simple repeats (teal), and low complexity regions (pale green) in intron 1, 1b, 9, 10, and 14 of (A)

The percent sequence coverage for each element over the entire region from is shown by open circl... more The percent sequence coverage for each element over the entire region from is shown by open circles. There was significantly less sequence masked by LTR and DNA elements in tammar compared to both mouse and human, while there was significantly more sequence occupied by low complexity regions (*). There was significantly less sequence occupied by LINEs in mouse compared to human (**). There was a large range in the sequence covered by LINEs in all species, but particularly in human and mouse. The percent sequence occupied by different types of repetitive elements in the region from , in all of , and in introns 9, 10, 1, 1b, and 14 assessed separately (B). The relative percentage of sequence occupied by LINEs is noticeably more than the percentage occupied by LINEs in any other intron from KCNQ1 and this increase was significant for mouse (*). No other significant differences in the relative amounts of sequence covered by different types of elements was seen between regions within spe...

Research paper thumbnail of Front & Back Matter

Research paper thumbnail of Front & Back Matter

Research paper thumbnail of Expression of STRA8 is conserved in therian mammals but expression of CYP26B1 differs between marsupials and mice

Biology of Reproduction, 2017

The first sign of mammalian germ cell sexual differentiation is the initiation of meiosis in fema... more The first sign of mammalian germ cell sexual differentiation is the initiation of meiosis in females and of mitotic arrest in males. In the mouse, retinoic acid induces ovarian Stra8 expression and entry of germ cells into meiosis. In developing mouse testes, cytochrome P450 family 26, subfamily b, polypeptide 1 (CYP26B1) produced by the Sertoli cells degrades retinoic acid, preventing Stimulated by Retinoic Acid Gene 8 (Stra8), expression and inhibiting meiosis. However, in developing humans, there is no evidence that CYP26B1 acts a meiosis-inhibiting factor. We therefore examined aspects of the retinoic acid/STRA8/CYP26B1 pathway during gonadal development in the tammar wallaby, a marsupial, to understand whether retinoic acid stimulation of STRA8 and CYP26B1 degradation of retinoic acid was conserved between widely divergent mammals. In tammar ovaries, as in human ovaries and unlike the pattern in mice, CYP26B1 expression was not downregulated before the onset of meiosis. Exposure of pre-meiotic tammar ovaries to exogenous retinoic acid in vitro upregulated STRA8 expression compared to controls. We conclude that retinoic acid and STRA8 are conserved factors that control the initiation of meiosis amongst mammals but the role of CYP26B1 as a meiosis-inhibiting factor may be specific to rodents. The identity of the marsupial meiosis-inhibiting factor remains unknown.

Research paper thumbnail of Embryonic Diapause and Maternal Recognition of Pregnancy in Diapausing Mammals

Regulation of Implantation and Establishment of Pregnancy in Mammals, 2015

The dynamic nature of early embryonic growth is at odds with the phenomenon of mammalian embryoni... more The dynamic nature of early embryonic growth is at odds with the phenomenon of mammalian embryonic diapause, because embryos in diapause are in a state of suspended animation of varying duration. The signals that control embryonic diapause differ between species, but in all cases, it acts to synchronise reproduction with external factors to maximise the survival of the offspring. This chapter provides an overview of current understanding of the control of embryonic diapause, with an emphasis on the three species about which most is known, namely, the mouse, the mink and the tammar wallaby.

Research paper thumbnail of DNA methylation dynamics in the germline of the marsupial tammar wallaby,Macropus eugenii

DNA Research, 2018

Parent specific-DNA methylation is the genomic imprint that induces mono-allelic gene expression ... more Parent specific-DNA methylation is the genomic imprint that induces mono-allelic gene expression dependent on parental origin. Resetting of DNA methylation in the germ line is mediated by a genome-wide re-methylation following demethylation known as epigenetic reprogramming. Most of our understanding of epigenetic reprogramming in germ cells is based on studies in mice, but little is known about this in marsupials. We examined genome-wide changes in DNA methylation levels by measuring 5-methylcytosine expression, and mRNA expression and protein localization of the key enzyme DNA methyltransferase 3 L (DNMT3L) during germ cell development of the marsupial tammar wallaby, Macropus eugenii. Our data clearly showed that the relative timing of genome-wide changes in DNA methylation was conserved between the tammar and mouse, but in the tammar it all occurred post-natally. In the female tammar, genome-wide demethylation occurred in two phases, I and II, suggesting that there is an unidentified demethylation mechanism in this species. Although the localization pattern of DNMT3L in male germ cells differed, the expression patterns of DNMT3L were broadly conserved between tammar, mouse and human. Thus, the basic mechanisms of DNA methylation-reprogramming must have been established before the marsupial-eutherian mammal divergence over 160 Mya.

Research paper thumbnail of HOXA13 and HOXD13 expression during development of the syndactylous digits in the marsupial Macropus eugenii

BMC Developmental Biology, 2011

BackgroundKangaroos and wallabies have specialised limbs that allow for their hopping mode of loc... more BackgroundKangaroos and wallabies have specialised limbs that allow for their hopping mode of locomotion. The hindlimbs differentiate much later in development but become much larger than the forelimbs. The hindlimb autopod has only four digits, the fourth of which is greatly elongated, while digits two and three are syndactylous. We investigated the expression of two genes, HOXA13 and HOXD13, that are crucial for digit patterning in mice during formation of the limbs of the tammar wallaby.ResultsWe describe the development of the tammar limbs at key stages before birth. There was marked heterochrony and the hindlimb developed more slowly than the forelimb. Both tammar HOXA13 and HOXD13 have two exons as in humans, mice and chickens. HOXA13 had an early and distal mRNA distribution in the tammar limb bud as in the mouse, but forelimb expression preceded that in the hindlimb. HOXD13 mRNA was expressed earlier in the forelimb than the hindlimb and was predominantly detected in the int...

Research paper thumbnail of A Guide to the care and use of Australian native mammals in research and teaching (2014). National Health and Medical Research Council

Research paper thumbnail of Reproductive physiology of marsupials: References

Research paper thumbnail of Insulin is imprinted in the placenta of the marsupial, Macropus eugenii

Developmental Biology, 2007

Research paper thumbnail of Characterisation of marsupial PHLDA2 reveals eutherian specific acquisition of imprinting

BMC Evolutionary Biology, 2011

Research paper thumbnail of Genomic structure of tammar IGF2 including 3 TSS and comparison with mouse, human and opossum genomes

<p>Opossum (clone XX-223O16 ch5∶102112-82113), human (ch11∶2156597-2176597) and mouse (ch7∶... more <p>Opossum (clone XX-223O16 ch5∶102112-82113), human (ch11∶2156597-2176597) and mouse (ch7∶149841559-149861559), <i>IGF2</i> base genomes were aligned to tammar <i>IGF2</i> (clone MEKBa-346C2∶62540-82539). VISTA pairwise alignments using a 100 bp sliding window was performed between each species and tammar. Pink peaks represent areas of conservation of 70% over a minimum of 100 bp between tammar and opossum and 55% over a minimum of 50 bp between tammar and human or mouse. A dotted line indicates a region with 70% conservation between P1 and P2 in both marsupials and eutherians. A schematic of each <i>IGF2</i> gene is located above the VISTA plot to show relative location of the non-coding exons (open box), including the non-coding exons transcribed with the P0 TSS <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0041690#pone.0041690-Monk1&quot; target="_blank">[12]</a>, and coding exons (black box). Location of CpG sites are represented by vertical black bars below the VISTA plot.</p

Research paper thumbnail of Placental imprinting of SLC22A3 in the IGF2R imprinted domain is conserved in therian mammals

Epigenetics & Chromatin

Background The eutherian IGF2R imprinted domain is regulated by an antisense long non-coding RNA,... more Background The eutherian IGF2R imprinted domain is regulated by an antisense long non-coding RNA, Airn, which is expressed from a differentially methylated region (DMR) in mice. Airn silences two neighbouring genes, Solute carrier family 22 member 2 (Slc22a2) and Slc22a3, to establish the Igf2r imprinted domain in the mouse placenta. Marsupials also have an antisense non-coding RNA, ALID, expressed from a DMR, although the exact function of ALID is currently unknown. The eutherian IGF2R DMR is located in intron 2, while the marsupial IGF2R DMR is located in intron 12, but it is not yet known whether the adjacent genes SLC22A2 and/or SLC22A3 are also imprinted in the marsupial lineage. In this study, the imprinting status of marsupial SLC22A2 and SLC22A3 in the IGF2R imprinted domain in the chorio-vitelline placenta was examined in a marsupial, the tammar wallaby. Results In the tammar placenta, SLC22A3 but not SLC22A2 was imprinted. Tammar SLC22A3 imprinting was evident in placental...

Research paper thumbnail of Reproductive physiology of marsupials: References

Research paper thumbnail of Molecular conservation of marsupial and eutherian placentation and lactation

eLife, 2017

Eutherians are often mistakenly termed ‘placental mammals’, but marsupials also have a placenta t... more Eutherians are often mistakenly termed ‘placental mammals’, but marsupials also have a placenta to mediate early embryonic development. Lactation is necessary for both infant and fetal development in eutherians and marsupials, although marsupials have a far more complex milk repertoire that facilitates morphogenesis of developmentally immature young. In this study, we demonstrate that the anatomically simple tammar placenta expresses a dynamic molecular program that is reminiscent of eutherian placentation, including both fetal and maternal signals. Further, we provide evidence that genes facilitating fetal development and nutrient transport display convergent co-option by placental and mammary gland cell types to optimize offspring success.

Research paper thumbnail of Evolution of the Short Form of DNMT3A, DNMT3A2, Occurred in the Common Ancestor of Mammals

Genome Biology and Evolution

Genomic imprinting is found in marsupial and eutherian mammals, but not in monotremes. While the ... more Genomic imprinting is found in marsupial and eutherian mammals, but not in monotremes. While the primary regulator of genomic imprinting in eutherians is differential DNA methylation between parental alleles, conserved imprinted genes in marsupials tend to lack DNA methylation at their promoters. DNA methylation at eutherian imprinted genes is mainly catalyzed by a DNA methyltransferase (DNMT) enzyme, DNMT3A. There are two isoforms of eutherian DNMT3A: DNMT3A and DNMT3A2. DNMT3A2 is the primary isoform for establishing DNA methylation at eutherian imprinted genes and is essential for eutherian genomic imprinting. In this study, we investigated whether DNMT3A2 is also present in the two other mammalian lineages, marsupials and monotremes. We identified DNMT3A2 in both marsupials and monotremes, although imprinting has not been identified in monotremes. By analyzing genomic sequences and transcriptome data across vertebrates, we concluded that the evolution of DNMT3A2 occurred in the ...

Research paper thumbnail of Evolution of the Short Form of DNMT3A, DNMT3A2, Occurred in the Common Ancestor of Mammals

Genome Biology and Evolution

Genomic imprinting is found in marsupial and eutherian mammals, but not in monotremes. While the ... more Genomic imprinting is found in marsupial and eutherian mammals, but not in monotremes. While the primary regulator of genomic imprinting in eutherians is differential DNA methylation between parental alleles, conserved imprinted genes in marsupials tend to lack DNA methylation at their promoters. DNA methylation at eutherian imprinted genes is mainly catalyzed by a DNA methyltransferase (DNMT) enzyme, DNMT3A. There are two isoforms of eutherian DNMT3A: DNMT3A and DNMT3A2. DNMT3A2 is the primary isoform for establishing DNA methylation at eutherian imprinted genes and is essential for eutherian genomic imprinting. In this study, we investigated whether DNMT3A2 is also present in the two other mammalian lineages, marsupials and monotremes. We identified DNMT3A2 in both marsupials and monotremes, although imprinting has not been identified in monotremes. By analyzing genomic sequences and transcriptome data across vertebrates, we concluded that the evolution of DNMT3A2 occurred in the ...

Research paper thumbnail of Intensity of staining to IGF2 and IGF2R antibodies in the yolk sac trophoblast during the final third of gestation (A)

The intensity of staining was measured subjectively as described in the experimental procedures. ... more The intensity of staining was measured subjectively as described in the experimental procedures. The bilaminar (BYS) (shaded bars) and trilaminar yolk sac (TYS) (open bars) of matched samples were assessed independently. Samples were grouped into days 19–21 (n = 4), 22–24 (n = 5), and 25–26 (n = 4). Staining intensity to the IGF2 antibody was consistently stronger in the TYS, especially at days 25–26. Staining by the IGF2 antibody was notably lighter at days 19–21 than later stages (days 22 to 26). Staining by the IGF2R antibody did not differ notably between the bilaminar and trilaminar yolk sac, nor were there marked differences corresponding to developmental stage. Intensity of staining by IGF2 and IGF2R antibodies in yolk sac cells (B). Staining intensity was noticeably higher in the trophoblast (Tr) (stippled bars) than in the yolk sac endoderm (En) (striped bars) of the bilaminar (BYS) and trilaminar (TYS) for IGF2, but not IGF2R. The staining intensity represents the average ...

Research paper thumbnail of Intensity of staining to IGF2 and IGF2R antibodies in the yolk sac trophoblast during the final third of gestation (A)

The intensity of staining was measured subjectively as described in the experimental procedures. ... more The intensity of staining was measured subjectively as described in the experimental procedures. The bilaminar (BYS) (shaded bars) and trilaminar yolk sac (TYS) (open bars) of matched samples were assessed independently. Samples were grouped into days 19–21 (n = 4), 22–24 (n = 5), and 25–26 (n = 4). Staining intensity to the IGF2 antibody was consistently stronger in the TYS, especially at days 25–26. Staining by the IGF2 antibody was notably lighter at days 19–21 than later stages (days 22 to 26). Staining by the IGF2R antibody did not differ notably between the bilaminar and trilaminar yolk sac, nor were there marked differences corresponding to developmental stage. Intensity of staining by IGF2 and IGF2R antibodies in yolk sac cells (B). Staining intensity was noticeably higher in the trophoblast (Tr) (stippled bars) than in the yolk sac endoderm (En) (striped bars) of the bilaminar (BYS) and trilaminar (TYS) for IGF2, but not IGF2R. The staining intensity represents the average ...

Research paper thumbnail of A box plot showing the percent of total sequence masked by SINEs (dark blue), LINEs (light blue), LTR elements (purple), DNA elements (pink), simple repeats (teal), and low complexity regions (pale green) in intron 1, 1b, 9, 10, and 14 of (A)

The percent sequence coverage for each element over the entire region from is shown by open circl... more The percent sequence coverage for each element over the entire region from is shown by open circles. There was significantly less sequence masked by LTR and DNA elements in tammar compared to both mouse and human, while there was significantly more sequence occupied by low complexity regions (*). There was significantly less sequence occupied by LINEs in mouse compared to human (**). There was a large range in the sequence covered by LINEs in all species, but particularly in human and mouse. The percent sequence occupied by different types of repetitive elements in the region from , in all of , and in introns 9, 10, 1, 1b, and 14 assessed separately (B). The relative percentage of sequence occupied by LINEs is noticeably more than the percentage occupied by LINEs in any other intron from KCNQ1 and this increase was significant for mouse (*). No other significant differences in the relative amounts of sequence covered by different types of elements was seen between regions within spe...

Research paper thumbnail of A box plot showing the percent of total sequence masked by SINEs (dark blue), LINEs (light blue), LTR elements (purple), DNA elements (pink), simple repeats (teal), and low complexity regions (pale green) in intron 1, 1b, 9, 10, and 14 of (A)

The percent sequence coverage for each element over the entire region from is shown by open circl... more The percent sequence coverage for each element over the entire region from is shown by open circles. There was significantly less sequence masked by LTR and DNA elements in tammar compared to both mouse and human, while there was significantly more sequence occupied by low complexity regions (*). There was significantly less sequence occupied by LINEs in mouse compared to human (**). There was a large range in the sequence covered by LINEs in all species, but particularly in human and mouse. The percent sequence occupied by different types of repetitive elements in the region from , in all of , and in introns 9, 10, 1, 1b, and 14 assessed separately (B). The relative percentage of sequence occupied by LINEs is noticeably more than the percentage occupied by LINEs in any other intron from KCNQ1 and this increase was significant for mouse (*). No other significant differences in the relative amounts of sequence covered by different types of elements was seen between regions within spe...

Research paper thumbnail of Front & Back Matter

Research paper thumbnail of Front & Back Matter

Research paper thumbnail of Expression of STRA8 is conserved in therian mammals but expression of CYP26B1 differs between marsupials and mice

Biology of Reproduction, 2017

The first sign of mammalian germ cell sexual differentiation is the initiation of meiosis in fema... more The first sign of mammalian germ cell sexual differentiation is the initiation of meiosis in females and of mitotic arrest in males. In the mouse, retinoic acid induces ovarian Stra8 expression and entry of germ cells into meiosis. In developing mouse testes, cytochrome P450 family 26, subfamily b, polypeptide 1 (CYP26B1) produced by the Sertoli cells degrades retinoic acid, preventing Stimulated by Retinoic Acid Gene 8 (Stra8), expression and inhibiting meiosis. However, in developing humans, there is no evidence that CYP26B1 acts a meiosis-inhibiting factor. We therefore examined aspects of the retinoic acid/STRA8/CYP26B1 pathway during gonadal development in the tammar wallaby, a marsupial, to understand whether retinoic acid stimulation of STRA8 and CYP26B1 degradation of retinoic acid was conserved between widely divergent mammals. In tammar ovaries, as in human ovaries and unlike the pattern in mice, CYP26B1 expression was not downregulated before the onset of meiosis. Exposure of pre-meiotic tammar ovaries to exogenous retinoic acid in vitro upregulated STRA8 expression compared to controls. We conclude that retinoic acid and STRA8 are conserved factors that control the initiation of meiosis amongst mammals but the role of CYP26B1 as a meiosis-inhibiting factor may be specific to rodents. The identity of the marsupial meiosis-inhibiting factor remains unknown.

Research paper thumbnail of Embryonic Diapause and Maternal Recognition of Pregnancy in Diapausing Mammals

Regulation of Implantation and Establishment of Pregnancy in Mammals, 2015

The dynamic nature of early embryonic growth is at odds with the phenomenon of mammalian embryoni... more The dynamic nature of early embryonic growth is at odds with the phenomenon of mammalian embryonic diapause, because embryos in diapause are in a state of suspended animation of varying duration. The signals that control embryonic diapause differ between species, but in all cases, it acts to synchronise reproduction with external factors to maximise the survival of the offspring. This chapter provides an overview of current understanding of the control of embryonic diapause, with an emphasis on the three species about which most is known, namely, the mouse, the mink and the tammar wallaby.

Research paper thumbnail of DNA methylation dynamics in the germline of the marsupial tammar wallaby,Macropus eugenii

DNA Research, 2018

Parent specific-DNA methylation is the genomic imprint that induces mono-allelic gene expression ... more Parent specific-DNA methylation is the genomic imprint that induces mono-allelic gene expression dependent on parental origin. Resetting of DNA methylation in the germ line is mediated by a genome-wide re-methylation following demethylation known as epigenetic reprogramming. Most of our understanding of epigenetic reprogramming in germ cells is based on studies in mice, but little is known about this in marsupials. We examined genome-wide changes in DNA methylation levels by measuring 5-methylcytosine expression, and mRNA expression and protein localization of the key enzyme DNA methyltransferase 3 L (DNMT3L) during germ cell development of the marsupial tammar wallaby, Macropus eugenii. Our data clearly showed that the relative timing of genome-wide changes in DNA methylation was conserved between the tammar and mouse, but in the tammar it all occurred post-natally. In the female tammar, genome-wide demethylation occurred in two phases, I and II, suggesting that there is an unidentified demethylation mechanism in this species. Although the localization pattern of DNMT3L in male germ cells differed, the expression patterns of DNMT3L were broadly conserved between tammar, mouse and human. Thus, the basic mechanisms of DNA methylation-reprogramming must have been established before the marsupial-eutherian mammal divergence over 160 Mya.

Research paper thumbnail of HOXA13 and HOXD13 expression during development of the syndactylous digits in the marsupial Macropus eugenii

BMC Developmental Biology, 2011

BackgroundKangaroos and wallabies have specialised limbs that allow for their hopping mode of loc... more BackgroundKangaroos and wallabies have specialised limbs that allow for their hopping mode of locomotion. The hindlimbs differentiate much later in development but become much larger than the forelimbs. The hindlimb autopod has only four digits, the fourth of which is greatly elongated, while digits two and three are syndactylous. We investigated the expression of two genes, HOXA13 and HOXD13, that are crucial for digit patterning in mice during formation of the limbs of the tammar wallaby.ResultsWe describe the development of the tammar limbs at key stages before birth. There was marked heterochrony and the hindlimb developed more slowly than the forelimb. Both tammar HOXA13 and HOXD13 have two exons as in humans, mice and chickens. HOXA13 had an early and distal mRNA distribution in the tammar limb bud as in the mouse, but forelimb expression preceded that in the hindlimb. HOXD13 mRNA was expressed earlier in the forelimb than the hindlimb and was predominantly detected in the int...

Research paper thumbnail of A Guide to the care and use of Australian native mammals in research and teaching (2014). National Health and Medical Research Council

Research paper thumbnail of Reproductive physiology of marsupials: References