The imprinted Zdbf2 gene finely tunes control of feeding and growth in neonates
Genomic imprinting refers to the mono-allelic and parent-specific expression of a subset of genes. While long recognized for their role in embryonic development, imprinted genes have recently emerged as important modulators of postnatal physiology, notably through hypothalamus-driven functions. Here...
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2022-01-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/65641 |
| _version_ | 1811227539404750848 |
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| author | Juliane Glaser Julian Iranzo Maud Borensztein Mattia Marinucci Angelica Gualtieri Colin Jouhanneau Aurélie Teissandier Carles Gaston-Massuet Deborah Bourc'his |
| author_facet | Juliane Glaser Julian Iranzo Maud Borensztein Mattia Marinucci Angelica Gualtieri Colin Jouhanneau Aurélie Teissandier Carles Gaston-Massuet Deborah Bourc'his |
| author_sort | Juliane Glaser |
| collection | DOAJ |
| description | Genomic imprinting refers to the mono-allelic and parent-specific expression of a subset of genes. While long recognized for their role in embryonic development, imprinted genes have recently emerged as important modulators of postnatal physiology, notably through hypothalamus-driven functions. Here, using mouse models of loss, gain and parental inversion of expression, we report that the paternally expressed Zdbf2 gene controls neonatal growth in mice, in a dose-sensitive but parent-of-origin-independent manner. We further found that Zdbf2-KO neonates failed to fully activate hypothalamic circuits that stimulate appetite, and suffered milk deprivation and diminished circulating Insulin Growth Factor 1 (IGF-1). Consequently, only half of Zdbf2-KO pups survived the first days after birth and those surviving were smaller. This study demonstrates that precise imprinted gene dosage is essential for vital physiological functions at the transition from intra- to extra-uterine life, here the adaptation to oral feeding and optimized body weight gain. |
| first_indexed | 2024-04-12T09:44:18Z |
| format | Article |
| id | doaj.art-4e59277598dd4ccbbd4bcaaa22690b54 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T09:44:18Z |
| publishDate | 2022-01-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-4e59277598dd4ccbbd4bcaaa22690b542022-12-22T03:37:59ZengeLife Sciences Publications LtdeLife2050-084X2022-01-011110.7554/eLife.65641The imprinted Zdbf2 gene finely tunes control of feeding and growth in neonatesJuliane Glaser0https://orcid.org/0000-0001-6745-6924Julian Iranzo1https://orcid.org/0000-0002-9369-2530Maud Borensztein2https://orcid.org/0000-0002-4378-5018Mattia Marinucci3Angelica Gualtieri4Colin Jouhanneau5Aurélie Teissandier6Carles Gaston-Massuet7Deborah Bourc'his8https://orcid.org/0000-0001-9499-7291Institut Curie, PSL Research University, INSERM, CNRS, Paris, FranceInstitut Curie, PSL Research University, INSERM, CNRS, Paris, FranceInstitut Curie, PSL Research University, INSERM, CNRS, Paris, FranceInstitut Curie, PSL Research University, INSERM, CNRS, Paris, FranceCentre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, United KingdomInstitut Curie, PSL Research University, Animal Transgenesis Platform, Paris, FranceInstitut Curie, PSL Research University, INSERM, CNRS, Paris, FranceCentre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, United KingdomInstitut Curie, PSL Research University, INSERM, CNRS, Paris, FranceGenomic imprinting refers to the mono-allelic and parent-specific expression of a subset of genes. While long recognized for their role in embryonic development, imprinted genes have recently emerged as important modulators of postnatal physiology, notably through hypothalamus-driven functions. Here, using mouse models of loss, gain and parental inversion of expression, we report that the paternally expressed Zdbf2 gene controls neonatal growth in mice, in a dose-sensitive but parent-of-origin-independent manner. We further found that Zdbf2-KO neonates failed to fully activate hypothalamic circuits that stimulate appetite, and suffered milk deprivation and diminished circulating Insulin Growth Factor 1 (IGF-1). Consequently, only half of Zdbf2-KO pups survived the first days after birth and those surviving were smaller. This study demonstrates that precise imprinted gene dosage is essential for vital physiological functions at the transition from intra- to extra-uterine life, here the adaptation to oral feeding and optimized body weight gain.https://elifesciences.org/articles/65641genomic imprintingdevelopmentgrowthhypothalamus |
| spellingShingle | Juliane Glaser Julian Iranzo Maud Borensztein Mattia Marinucci Angelica Gualtieri Colin Jouhanneau Aurélie Teissandier Carles Gaston-Massuet Deborah Bourc'his The imprinted Zdbf2 gene finely tunes control of feeding and growth in neonates eLife genomic imprinting development growth hypothalamus |
| title | The imprinted Zdbf2 gene finely tunes control of feeding and growth in neonates |
| title_full | The imprinted Zdbf2 gene finely tunes control of feeding and growth in neonates |
| title_fullStr | The imprinted Zdbf2 gene finely tunes control of feeding and growth in neonates |
| title_full_unstemmed | The imprinted Zdbf2 gene finely tunes control of feeding and growth in neonates |
| title_short | The imprinted Zdbf2 gene finely tunes control of feeding and growth in neonates |
| title_sort | imprinted zdbf2 gene finely tunes control of feeding and growth in neonates |
| topic | genomic imprinting development growth hypothalamus |
| url | https://elifesciences.org/articles/65641 |
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