Abca4, mutated in Stargardt disease, is required for structural integrity of cone outer segments.

Stargardt disease (STGD), the leading cause of inherited childhood blindness, is primarily caused by mutations in the ABCA4 gene; yet, the underlying mechanisms of photoreceptor degeneration remain elusive, partly due to limitations in existing animal disease models. To expand our understanding, we mutated the human ABCA4 paralogues abca4a and abca4b in zebrafish, which has a cone-rich retina. Our study unveiled striking dysmorphology and elongation of cone outer segments (COS) in abca4a;abca4b double mutants, alongside reduced phagocytosis by the retinal pigmented epithelium (RPE).

Two types of transgenic lines for doxycycline-inducible, cell-specific gene expression in zebrafish ultraviolet cone photoreceptors.

Temporal and spatial control of gene expression is important for studying the molecular and cellular mechanisms of development, physiology, and disease. We used the doxycycline (Dox)-inducible, Tet-On system to develop transgenic zebrafish for inducible, cell specific control of gene expression in the ultraviolet (UV) cone photoreceptors. Two constructs containing the reverse tetracycline-controlled transcriptional transactivator (rtTA) gene driven by the UV opsin-specific promoter (opn1sw1) were used to generate stable transgenic zebrafish lines using the Tol2-based transgenesis method.

Two types of Tet-On transgenic lines for doxycycline-inducible gene expression in zebrafish rod photoreceptors and a gateway-based tet-on toolkit.

The ability to control transgene expression within specific tissues is an important tool for studying the molecular and cellular mechanisms of development, physiology, and disease. We developed a Tet-On system for spatial and temporal control of transgene expression in zebrafish rod photoreceptors. We generated two transgenic lines using the Xenopus rhodopsin promoter to drive the reverse tetracycline-controlled transcriptional transactivator (rtTA), one with self-reporting GFP activity and one with an epitope tagged rtTA.

Generation of a genetically encoded marker of rod photoreceptor outer segment growth and renewal.

Vertebrate photoreceptors are specialized light sensing neurons. The photoreceptor outer segment is a highly modified cilium where photons of light are transduced into a chemical and electrical signal. The outer segment has the typical cilary axoneme but, in addition, it has a large number of densely packed, stacked, intramembranous discs.

Mosaic Eyes is a novel component of the Crumbs complex and negatively regulates photoreceptor apical size.

Establishment of apical-basal cell polarity has emerged as an important process during development, and the Crumbs complex is a major component of this process in Drosophila. By comparison, little is known about the role of Crumbs (Crb) proteins in vertebrate development. We show that the FERM protein Mosaic Eyes (Moe) is a novel regulatory component of the Crumbs complex.