Neuro-Development Lab

CGE Lab Photo 2012

CGE Lab Photo 2012


The Gregory-Evans Neuro-Development Lab undertakes studies in ocular development, in zebrafish and mouse models of eye disease.

Ocular coloboma

Role of Fadd in optic fissure closure. Fadd is an adaptor protein involved in the induction of cell death. This project looks at the role of cell death in normal optic fissure morphogenesis and what happens when the balance between cell death and cell proliferation is disrupted. We are using morpholino gene knockdown and cell death/proliferation assays to investigate these processes.

Identification of the downstream targets of the Pax2 transcription factor. Although mutations in many different transcription factors cause ocular coloboma, how they lead to failure of optic fissure closure at the cellular level is unknown. This projects is aimed at finding the transcriptional targets of Pax2 and to determine how they influence epithelial fusion at the optic fissure, using techniques such as ChIP-seq and expression profiling in the pax2-deficient zebrafish model.

Modelling human chromosomal deletions and insertions that cause multiple tissue fusion defects. Chromosomal abnormalities in patients with multiple fusion defects such as coloboma, neural tube defects, palate/lip defects and ventricular septum defects usually affect more than one gene. To determine which of the genes in a deletion is important for example, we use antisense morpholino knockdown to see which genes cause a fusion defect.

In wildtype (WT) zebrafish eyes the optic fissure is closed at 48 hpf, but when Fadd is knocked down using morpholinos (MO) the optic fissure is still open at 48 hpf. In WT eyes there is little PH3 labelling (a proliferation marker) but in the Pax2 mutant zebrafish, there is an open fissure and excessive proliferation. When Fadd mRNA is injected into Pax2 -deficient embryos the optic fissure closes and the proliferation is markedly reduced, demonstrating that Fadd is a direct downstream target of Pax2 (Viringipurampeer IA et al, 2012. Hum Mol Genet . 21:2357-2369).

In wildtype (WT) zebrafish eyes the optic fissure is closed at 48 hpf, but when Fadd is knocked down using morpholinos (MO) the optic fissure is still open at 48 hpf. In WT eyes there is little PH3 labelling (a proliferation marker) but in the Pax2 mutant zebrafish, there is an open fissure and excessive proliferation. When Fadd mRNA is injected into Pax2 -deficient embryos the optic fissure closes and the proliferation is markedly reduced, demonstrating that Fadd is a direct downstream target of Pax2 (Viringipurampeer IA et al, 2012. Hum Mol Genet . 21:2357-2369).

Drug screening in zebrafish with retinal dystrophy

The etiology of Pde6c mutation causing cone photoreceptor cell death. To understand how mutations in PDE6C cause achromatopsia (complete colour blindness) in humans, we are investigating which cell death pathways are activated in cone cells. The Pde6c zebrafish model is being used to test novel therapies for this disease.

 Small molecule therapeutics in zebrafish models of anterior segment dysgenesis.

Small molecule therapeutics in zebrafish models of anterior segment dysgenesis.

Aniridia

Identification of the downstream targets of the Pax6 transcription factor. A classic feature of aniridia is partial or complete absence of the iris tissue. To determine how Pax6 drives normal iris development we are using both mouse and zebrafish models of aniridia to find the Pax6 targets that drive tissue morphogenesis. To do this we are using laser-capture microdissection and gene expression profiling in these model systems.

Foveal hypoplasia in aniridia. A common finding in aniridia is the underdevelopment of the foveal region of the retina, that is important for high visual acuity and colour vision. We are using high resolution optical coherence tomography to investigate the abnormalities in patients with aniridia and studying the normal pathway leading to foveal specialization in the retina that occurs up to 4 years of age.

 Anatomical defects in the developing mouse eye caused by Pax6 heterozygous mutation. At E12.5 the lens has not separated from the corneal epithelium. At E14.5 the retina is proliferating and distending into the vitreous. At E16.5 the whole eye and lens is smaller and retinal development is immature.

Anatomical defects in the developing mouse eye caused by Pax6 heterozygous mutation. At E12.5 the lens has not separated from the corneal epithelium. At E14.5 the retina is proliferating and distending into the vitreous. At E16.5 the whole eye and lens is smaller and retinal development is immature.

Past & Present Lab Members

Graduate students

Naif Sannan (2012-present)
Elham Mohammadi (2011-present)
Nir Grossman (2008-2010)
Mariya Moosajee (2005-2009)
Merrin Tulloch (2003-2008)
James Blackburn (2000-2004)
Helena Vieira (2000-2003)
Lindsay Bibb (1998-2002)

Post-doctoral Research Associates

Ishaq Viringipurampeer (2010-present)
Xia Wang (2010-present)
Jiang Ping Zhang (2010-2011)
Matthew Williams (2003-2005)
Matthew Hodges (1999-2002)
Emma Tarttelin (1999-2002)
James Bellingham (1998-2000)

Research assistants

Xianghong Shan (2009-present)
Kelvin Po (2009)
Jookyung Justin Yoon (Co-op student 2011)
Bogdan Dascalu (Medical student 2010)

Collaborators

International:

Dr. David Cobrinik (Memorial-Sloan-Kettering Cancer Centre, NY, USA)
Dr. John Ngai (UC Berkeley, CA, USA)
Dr. Paul Denny (Mammalian Genetics Unit, UK)

National:

Dr. Patrice Eydoux (Women’s and Children’s Hospital, Vancouver)
Dr. Joy Richman (Faculty of Dentistry, UBC)
Dr. Kevin Gregory-Evans (Dept of Ophthalmology UBC)
Dr. Joanne Matsubara (Dept of Ophthalmology UBC)
Dr. Orson Moritz (Dept of Ophthalmology UBC)
Dr. Kishor Wasan (Faculty of Pharmaceutical Sciences, UBC)