When and how do faults in the YAP gene lead to coloboma?

Research details

  • Type of funding: PhD Studentship
  • Grant Holder: Professor Stephen Wilson
  • Institute: University College London
  • Region: London
  • Start date: October 2016
  • End Date: September 2019
  • Priority: Causes
  • Eye Category: Childhood-onset


Coloboma is a condition in which the eye does not form correctly as an embryo develops, leaving a gap that can cause severe sight loss. Specific genetic faults in a gene called YAP lead to coloboma in both humans and zebrafish, but we don’t know exactly why.

It’s hard to study embryonic development in mammals but it’s possible to see what’s happening clearly in zebrafish. So in this project the student will use genetic analysis and high-resolution imaging to study the process as the eye develops. The team wants to know exactly when and why faults in the YAP gene lead to coloboma, for example is there a critical window of time in which the developing eye is especially sensitive and are there any other genes that are involved? Results from the study could provide important information for families with genetic faults that increase the risk of having children with coloboma.

  • Scientific summary

    Genetic and cellular mechanisms underlying Yap-dependent coloboma

    Coloboma is a condition resulting from a failure in the correct morphogenesis of the eye during embryonic development. As the neuroepithelium of the eye takes shape, it forms a cup with a ventral opening called the choroid fissure. If this fissure fails to fuse closed, then a condition called coloboma arises, resulting in impaired vision or blindness. We know relatively little about the genetic regulation and cell/tissue biology of eye morphogenesis and it is this paucity of knowledge that this studentship project aims to address. In both humans and in zebrafish, specific mutations in a gene called Yap result in coloboma but we do not know why this happens.

    Yap is a transcriptional regulator in a highly conserved signalling pathway and so the student is performing experiments in zebrafish to resolve why compromised Yap function disrupts eye morphogenesis and can lead to coloboma. For instance, they will resolve in which cell type and at what developmental stage Yap function is required through the use of a temperature sensitive allele and cell-type specific transgenes. They will also resolve the mechanistic basis for the phenotypic defect by imaging the altered behaviours of retinal cells when Yap is compromised. The study will also provide additional information on other genetic regulators that when disrupted lead to eye abnormalities and visual deficits. Overall the studentship research will provide outstanding training opportunities through research that will resolve the role of a key regulator of eye morphogenesis.