The p2 progenitor domain in the ventral spinal cord gives rise to two interneuron subtypes: V2a and V2b. Delta-Notch-mediated cell-cell interactions between postmitotic immature neurons have been implicated in the segregation of neuron subtypes. However, lineage relationships between V2a and V2b neurons have not been reported. We address this issue using Tg[vsx1:GFP] zebrafish, a model system i...

Multipotent progenitors in the vertebrate retina often generate clonally related mixtures of excitatory and inhibitory neurons. The postmitotically expressed transcription factor, Ptf1a, is essential for all inhibitory fates in the zebrafish retina, including three types of horizontal and 28 types of amacrine cell. Here, we show that specific types of inhibitory neurons arise from the cell-auto...

Ribeye is the only known protein specific to synaptic ribbon, but its function is unclear. We show that the teleost fish, Fugu and zebrafish, have two ribeye genes, ribeye a and ribeye b. Whole-mount in situ hybridization revealed that ribeye a is expressed in tissues containing synaptic ribbons, including the pineal gland, inner ear, and retina. Ribeye b is absent in the pineal gland. In the r...

Rod-derived Cone Viability Factor (RdCVF) is a trophic factor with therapeutic potential for the treatment of retinitis pigmentosa, a retinal disease that commonly results in blindness. RdCVF is encoded by Nucleoredoxin-like 1 (Nxnl1), a gene homologous with the family of thioredoxins that participate in the defense against oxidative stress. RdCVF expression is lost after rod degeneration in th...

K eratoconus (OMIM148300) is a bilateral, non-inflammatory, slowly progressive, corneal ectasia that is a major cause of corneal transplant. Characteristically, the cornea becomes thin and conical, with myopia and irregular astigmatism that leads to vision impairment. The incidence of keratoconus is between 50 and 230 per 100 000, with remarkable differences between ethnic groups. Although the ...

PURPOSE Posterior Polymorphous Dystrophy (PPCD) is a genetically heterogeneous corneal dystrophy, with linkage to three different chromosomal loci, with several genes in these loci being implicated. The role of both VSX1 and COL8A2 in PPCD remains controversial but recent work suggests that mutations in the transcription factor gene ZEB1/TCF8 account for disease in up to 30% of subjects, with a...

We were very interested to read of a second mutation in the seed region of miR-184 resulting in EDICT syndrome. We were unsure after reading the paper, however, of how the corneal findings should be classified and of the statement that the family “does not demonstrate a keratoconus phenotype.” Keratoconus, the commonest disorder of corneal thinning and steepening, has been linked with VSX1 and ...

PURPOSE The photoreceptor conserved element-1 (PCE-1) sequence is found in the transcriptional regulatory regions of many genes expressed in photoreceptors. The retinal homeobox (Rx or Rax) gene product functions by binding to PCE-1 sites. However, other transcriptional regulators have also been reported to bind to PCE-1. One of these, vsx2, is expressed in retinal progenitor and bipolar cells....

PURPOSE To identify the genetic basis of posterior polymorphous corneal dystrophy 1 (PPCD1) using next-generation sequencing (NGS) of the common PPCD1 support interval, in which Sanger sequencing failed to identify a pathogenic mutation. METHODS Enrichment of the portion of chromosome 20 containing the common PPCD1 interval was performed on DNA extracted from an affected and an unaffected mem...

Whereas the mammalian retina possesses a repertoire of factors known to establish general retinal cell types, these factors alone cannot explain the vast diversity of neuronal subtypes. In other CNS regions, the differentiation of diverse neuronal pools is governed by coordinately acting LIM-homeodomain proteins including the Islet-class factor Islet-1 (Isl1). We report that deletion of Isl1 pr...