Tbx6 controls left-right asymmetry through regulation of Gdf1
The Tbx6 transcription factor plays multiple roles during gastrulation, somite formation and body axis determination. One of the notable features of the Tbx6 homozygous mutant phenotype is randomization of left/right axis determination. Cilia of the node are morphologically abnormal, leading to the...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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The Company of Biologists
2018-05-01
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| Series: | Biology Open |
| Subjects: | |
| Online Access: | http://bio.biologists.org/content/7/5/bio032565 |
| _version_ | 1818656680267743232 |
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| author | Daniel Concepcion Hiroshi Hamada Virginia E. Papaioannou |
| author_facet | Daniel Concepcion Hiroshi Hamada Virginia E. Papaioannou |
| author_sort | Daniel Concepcion |
| collection | DOAJ |
| description | The Tbx6 transcription factor plays multiple roles during gastrulation, somite formation and body axis determination. One of the notable features of the Tbx6 homozygous mutant phenotype is randomization of left/right axis determination. Cilia of the node are morphologically abnormal, leading to the hypothesis that disrupted nodal flow is the cause of the laterality defect. However, Tbx6 is expressed around but not in the node, leading to uncertainty as to the mechanism of this effect. In this study, we have examined the molecular characteristics of the node and the genetic cascade determining left/right axis determination. We found evidence that a leftward nodal flow is generated in Tbx6 homozygous mutants despite the cilia defect, establishing the initial asymmetric gene expression in Dand5 around the node, but that the transduction of the signal from the node to the left lateral plate mesoderm is disrupted due to lack of expression of the Nodal coligand Gdf1 around the node. Gdf1 was shown to be a downstream target of Tbx6 and a Gdf1 transgene partially rescues the laterality defect. |
| first_indexed | 2024-12-17T03:29:26Z |
| format | Article |
| id | doaj.art-75442cf36cd64a369345b04327185489 |
| institution | Directory Open Access Journal |
| issn | 2046-6390 |
| language | English |
| last_indexed | 2024-12-17T03:29:26Z |
| publishDate | 2018-05-01 |
| publisher | The Company of Biologists |
| record_format | Article |
| series | Biology Open |
| spelling | doaj.art-75442cf36cd64a369345b043271854892022-12-21T22:05:18ZengThe Company of BiologistsBiology Open2046-63902018-05-017510.1242/bio.032565032565Tbx6 controls left-right asymmetry through regulation of Gdf1Daniel Concepcion0Hiroshi Hamada1Virginia E. Papaioannou2 Department of Genetics and Development, Columbia University Medical Center, New York, NY 10032, USA RIKEN Center for Biosystems Dynamics Research, Kobe, 650-0047, Japan Department of Genetics and Development, Columbia University Medical Center, New York, NY 10032, USA The Tbx6 transcription factor plays multiple roles during gastrulation, somite formation and body axis determination. One of the notable features of the Tbx6 homozygous mutant phenotype is randomization of left/right axis determination. Cilia of the node are morphologically abnormal, leading to the hypothesis that disrupted nodal flow is the cause of the laterality defect. However, Tbx6 is expressed around but not in the node, leading to uncertainty as to the mechanism of this effect. In this study, we have examined the molecular characteristics of the node and the genetic cascade determining left/right axis determination. We found evidence that a leftward nodal flow is generated in Tbx6 homozygous mutants despite the cilia defect, establishing the initial asymmetric gene expression in Dand5 around the node, but that the transduction of the signal from the node to the left lateral plate mesoderm is disrupted due to lack of expression of the Nodal coligand Gdf1 around the node. Gdf1 was shown to be a downstream target of Tbx6 and a Gdf1 transgene partially rescues the laterality defect.http://bio.biologists.org/content/7/5/bio032565Tbx6Gdf1Left-right asymmetryMouse developmentAxis determination |
| spellingShingle | Daniel Concepcion Hiroshi Hamada Virginia E. Papaioannou Tbx6 controls left-right asymmetry through regulation of Gdf1 Biology Open Tbx6 Gdf1 Left-right asymmetry Mouse development Axis determination |
| title | Tbx6 controls left-right asymmetry through regulation of Gdf1 |
| title_full | Tbx6 controls left-right asymmetry through regulation of Gdf1 |
| title_fullStr | Tbx6 controls left-right asymmetry through regulation of Gdf1 |
| title_full_unstemmed | Tbx6 controls left-right asymmetry through regulation of Gdf1 |
| title_short | Tbx6 controls left-right asymmetry through regulation of Gdf1 |
| title_sort | tbx6 controls left right asymmetry through regulation of gdf1 |
| topic | Tbx6 Gdf1 Left-right asymmetry Mouse development Axis determination |
| url | http://bio.biologists.org/content/7/5/bio032565 |
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