Investigation of the role of primary cilia during signalling events in development using the chicken mutant talpid 3
Lead Research Organisation:
Roslin Institute
Department Name: UNLISTED
Abstract
Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.
Technical Summary
Talpid3 is an embryonically lethal chicken mutation. The phenotype is pleiotropic and includes limb polydactyly (many digits), facial and vascular defects and failure to form bone. We will build on recent progress in mapping the talpid3 mutation and identify the talpid3 gene. This gene is of fundamental importance because in this mutant all Hedgehog signalling is disrupted. Hedgehogs are a major class of extracellular signalling molecules, implicated in cell differentiation and survival both in embryos and tumours. Talpid3 limbs have many digits with no anterior-posterior pattern. We will exploit chicken genome resources and microarray technology to make comprehensive comparison of patterns of gene expression in normal and talpid3 limb buds. This will identify target genes downstream of the talpid3 gene and also identify new genes involved in anterior-posterior limb patterning.
Planned Impact
unavailable
People |
ORCID iD |
| Megan Davey (Principal Investigator) |
Publications
Bangs F
(2009)
16-P002 The developmental mutant talpid3 lacks primary cilia
in Mechanisms of Development
Burns A
(2009)
13-P093 Defects in gut and enteric nervous system development in talpid3 mutant chicken
in Mechanisms of Development
Davey MG
(2014)
Loss of cilia causes embryonic lung hypoplasia, liver fibrosis, and cholestasis in the talpid3 ciliopathy mutant.
in Organogenesis
May-Simera HL
(2016)
Loss of MACF1 Abolishes Ciliogenesis and Disrupts Apicobasal Polarity Establishment in the Retina.
in Cell reports
Pinkham J
(2009)
11-P012 Left/right axis specification in the cilia mutant talpid3
in Mechanisms of Development
Schock EN
(2016)
Utilizing the chicken as an animal model for human craniofacial ciliopathies.
in Developmental biology
Stephen LA
(2014)
The chicken left right organizer has nonmotile cilia which are lost in a stage-dependent manner in the talpid(3) ciliopathy.
in Genesis (New York, N.Y. : 2000)
Yin Y
(2009)
The Talpid3 gene (KIAA0586) encodes a centrosomal protein that is essential for primary cilia formation.
in Development (Cambridge, England)
| Description | The chicken talpid3 mutant, which have a mutation in TALPID3 lack primary cilia, a small organelle found on the surface of each cell. As primary cilia are important in embryo development, we found that a loss of primary cilia in causes defects in bone, liver and left/right axis specification. |
| Exploitation Route | The findings have already supported further funding in which we identified that TALPID3 mutations cause human ciliopathy conditions. |
| Sectors | Healthcare Pharmaceuticals and Medical Biotechnology |
| Description | TALPID3 mutations have been found to cause human Joubert Syndrome. Pre-implanation diagnosis has now been used to select human embryos who do not carry TALPID3 mutations in affected Joubert syndrome families. |
| First Year Of Impact | 2015 |
| Sector | Pharmaceuticals and Medical Biotechnology |
| Impact Types | Policy & public services |
| Description | Nordic Centrosome and Cilia Network |
| Organisation | Nordic Cilia and Centrosome Network |
| Country | Global |
| Sector | Charity/Non Profit |
| PI Contribution | Training partnerships, conferences |
| Collaborator Contribution | Training partnerships, conferences |
| Impact | Training[ proteomics |
| Start Year | 2012 |
| Description | Nuffield Research Placement |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | Yes |
| Geographic Reach | National |
| Primary Audience | Schools |
| Results and Impact | Encouraged STEM careers Students went on to take STEM subjects at university |
| Year(s) Of Engagement Activity | 2009,2010,2011,2012,2013,2014 |