Differential Requirement of Gata2a and Gata2b for Primitive and Definitive Myeloid Development in Zebrafish
Germline loss or mutation of one copy of the transcription factor GATA2 in humans leads to a range of clinical phenotypes affecting hematopoietic, lymphatic and vascular systems. GATA2 heterozygous mice show only a limited repertoire of the features observed in humans. Zebrafish have two copies of t...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-09-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2021.708113/full |
| _version_ | 1818576913842569216 |
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| author | Oscar A. Peña Alexandra Lubin Jasmine Rowell Yvette Hoade Noreen Khokhar Hanna Lemmik Christopher Mahony Phoebe Dace Chianna Umamahesan Elspeth M. Payne Elspeth M. Payne |
| author_facet | Oscar A. Peña Alexandra Lubin Jasmine Rowell Yvette Hoade Noreen Khokhar Hanna Lemmik Christopher Mahony Phoebe Dace Chianna Umamahesan Elspeth M. Payne Elspeth M. Payne |
| author_sort | Oscar A. Peña |
| collection | DOAJ |
| description | Germline loss or mutation of one copy of the transcription factor GATA2 in humans leads to a range of clinical phenotypes affecting hematopoietic, lymphatic and vascular systems. GATA2 heterozygous mice show only a limited repertoire of the features observed in humans. Zebrafish have two copies of the Gata2 gene as a result of an additional round of ancestral whole genome duplication. These genes, Gata2a and Gata2b, show distinct but overlapping expression patterns, and between them, highlight a significantly broader range of the phenotypes observed in GATA2 deficient syndromes, than each one alone. In this manuscript, we use mutants for Gata2a and Gata2b to interrogate the effects on hematopoiesis of these two ohnologs, alone and in combination, during development in order to further define the role of GATA2 in developmental hematopoiesis. We define unique roles for each ohnolog at different stages of developmental myelopoiesis and for the emergence of hematopoietic stem and progenitor cells. These effects are not additive in the haploinsufficient state suggesting a redundancy between these two genes in hematopoietic stem and progenitor cells. Rescue studies additionally support that Gata2b can compensate for the effects of Gata2a loss. Finally we show that adults with loss of combined heterozygosity show defects in the myeloid compartment consistent with GATA2 loss in humans. These results build on existing knowledge from other models of GATA2 deficiency and refine our understanding of the early developmental effects of GATA2. In addition, these studies shed light on the complexity and potential structure-function relationships as well as sub-functionalization of Gata2 genes in the zebrafish model. |
| first_indexed | 2024-12-16T06:21:35Z |
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| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-12-16T06:21:35Z |
| publishDate | 2021-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-024e03d57978457a9084fb5f7643a44d2022-12-21T22:41:06ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2021-09-01910.3389/fcell.2021.708113708113Differential Requirement of Gata2a and Gata2b for Primitive and Definitive Myeloid Development in ZebrafishOscar A. Peña0Alexandra Lubin1Jasmine Rowell2Yvette Hoade3Noreen Khokhar4Hanna Lemmik5Christopher Mahony6Phoebe Dace7Chianna Umamahesan8Elspeth M. Payne9Elspeth M. Payne10Research Department of Haematology, Cancer Institute, University College London, London, United KingdomResearch Department of Haematology, Cancer Institute, University College London, London, United KingdomResearch Department of Haematology, Cancer Institute, University College London, London, United KingdomResearch Department of Haematology, Cancer Institute, University College London, London, United KingdomResearch Department of Haematology, Cancer Institute, University College London, London, United KingdomResearch Department of Haematology, Cancer Institute, University College London, London, United KingdomDepartment of Pathology and Immunology, School of Medicine, University of Geneva, Geneva, SwitzerlandResearch Department of Haematology, Cancer Institute, University College London, London, United KingdomResearch Department of Haematology, Cancer Institute, University College London, London, United KingdomResearch Department of Haematology, Cancer Institute, University College London, London, United KingdomNational Institute for Health Research (NIHR)/UCLH Clinical Research Facility, University College London Hospitals NHS Foundation Trust, London, United KingdomGermline loss or mutation of one copy of the transcription factor GATA2 in humans leads to a range of clinical phenotypes affecting hematopoietic, lymphatic and vascular systems. GATA2 heterozygous mice show only a limited repertoire of the features observed in humans. Zebrafish have two copies of the Gata2 gene as a result of an additional round of ancestral whole genome duplication. These genes, Gata2a and Gata2b, show distinct but overlapping expression patterns, and between them, highlight a significantly broader range of the phenotypes observed in GATA2 deficient syndromes, than each one alone. In this manuscript, we use mutants for Gata2a and Gata2b to interrogate the effects on hematopoiesis of these two ohnologs, alone and in combination, during development in order to further define the role of GATA2 in developmental hematopoiesis. We define unique roles for each ohnolog at different stages of developmental myelopoiesis and for the emergence of hematopoietic stem and progenitor cells. These effects are not additive in the haploinsufficient state suggesting a redundancy between these two genes in hematopoietic stem and progenitor cells. Rescue studies additionally support that Gata2b can compensate for the effects of Gata2a loss. Finally we show that adults with loss of combined heterozygosity show defects in the myeloid compartment consistent with GATA2 loss in humans. These results build on existing knowledge from other models of GATA2 deficiency and refine our understanding of the early developmental effects of GATA2. In addition, these studies shed light on the complexity and potential structure-function relationships as well as sub-functionalization of Gata2 genes in the zebrafish model.https://www.frontiersin.org/articles/10.3389/fcell.2021.708113/fullGata2aGata2bhematopoiesisstem cellmyelopoiesis |
| spellingShingle | Oscar A. Peña Alexandra Lubin Jasmine Rowell Yvette Hoade Noreen Khokhar Hanna Lemmik Christopher Mahony Phoebe Dace Chianna Umamahesan Elspeth M. Payne Elspeth M. Payne Differential Requirement of Gata2a and Gata2b for Primitive and Definitive Myeloid Development in Zebrafish Frontiers in Cell and Developmental Biology Gata2a Gata2b hematopoiesis stem cell myelopoiesis |
| title | Differential Requirement of Gata2a and Gata2b for Primitive and Definitive Myeloid Development in Zebrafish |
| title_full | Differential Requirement of Gata2a and Gata2b for Primitive and Definitive Myeloid Development in Zebrafish |
| title_fullStr | Differential Requirement of Gata2a and Gata2b for Primitive and Definitive Myeloid Development in Zebrafish |
| title_full_unstemmed | Differential Requirement of Gata2a and Gata2b for Primitive and Definitive Myeloid Development in Zebrafish |
| title_short | Differential Requirement of Gata2a and Gata2b for Primitive and Definitive Myeloid Development in Zebrafish |
| title_sort | differential requirement of gata2a and gata2b for primitive and definitive myeloid development in zebrafish |
| topic | Gata2a Gata2b hematopoiesis stem cell myelopoiesis |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2021.708113/full |
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