Photoreceptor calyceal processes accompany the developing outer segment, adopting a stable length despite a dynamic core.

Vertebrate photoreceptors detect light through a large cilium-based outer segment, which is filled with photopigment-laden membranous discs. Surrounding the base of the outer segment are microvilli-like calyceal processes (CPs). Although CP disruption has been associated with altered outer segment morphology and photoreceptor degeneration, the role of the CPs remains elusive.

The inner junction protein CFAP20 functions in motile and non-motile cilia and is critical for vision.

Motile and non-motile cilia are associated with mutually-exclusive genetic disorders. Motile cilia propel sperm or extracellular fluids, and their dysfunction causes primary ciliary dyskinesia. Non-motile cilia serve as sensory/signalling antennae on most cell types, and their disruption causes single-organ ciliopathies such as retinopathies or multi-system syndromes.

The morphological and functional diversity of apical microvilli.

Sensory neurons use specialized apical processes to perceive external stimuli and monitor internal body conditions. The apical apparatus can include cilia, microvilli, or both, and is adapted for the functions of the particular cell type. Photoreceptors detect light through a large, modified cilium (outer segment), that is supported by a surrounding ring of microvilli-like calyceal processes (CPs).

Zebrafish and inherited photoreceptor disease: Models and insights.

Photoreceptor dysfunctions and degenerative diseases are significant causes of vision loss in patients, with few effective treatments available. Targeted interventions to prevent or reverse photoreceptor-related vision loss are not possible without a thorough understanding of the underlying mechanism leading to disease, which is exceedingly difficult to accomplish in the human system. Cone diseases are particularly challenging to model, as some popular genetically modifiable model animals are nocturnal with a rod-dominant visual system and cones that have dissimilarities to human cones.

A cell atlas of microbe-responsive processes in the zebrafish intestine.

Gut microbial products direct growth, differentiation, and development in animal hosts. However, we lack system-wide understanding of cell-specific responses to the microbiome. We profiled cell transcriptomes from the intestine, and associated tissue, of zebrafish larvae raised in the presence or absence of a microbiome.

Progressive Photoreceptor Dysfunction and Age-Related Macular Degeneration-Like Features in Mutant Zebrafish.

Photoreceptor disease results in irreparable vision loss and blindness, which has a dramatic impact on quality of life. Pathogenic mutations in lead to photoreceptor degenerations such as occult macular dystrophy and retinitis pigmentosa. RP1L1 is a component of the photoreceptor axoneme, the backbone structure of the photoreceptor's light-sensing outer segment.

Electroretinogram analysis of zebrafish retinal function across development.

Purpose: The electroretinogram (ERG) is a powerful approach for investigating visual function in zebrafish ocular disease models. However, complexity, cost, and a literature gap present as significant barriers for the introduction of this technology to new zebrafish laboratories. Here, we introduce a simplified and effective method to obtain zebrafish ERGs.

Abnormal Cone and Rod Photoreceptor Morphogenesis in gdf6a Mutant Zebrafish.

Purpose: Analysis of photoreceptor morphology and gene expression in mispatterned eyes of zebrafish growth differentiation factor 6a (gdf6a) mutants.

Methods: Rod and cone photoreceptors were compared between gdf6a mutant and control zebrafish from larval to late adult stages using transgenic labels, immunofluorescence, and confocal microscopy, as well as by transmission electron microscopy. To compare transcriptomes between larval gdf6a mutant and control zebrafish, RNA-Seq was performed on isolated eyes.

Visualization of the Superior Ocular Sulcus during Danio rerio Embryogenesis.

Congenital ocular coloboma is a genetic disorder that is typically observed as a cleft in the inferior aspect of the eye resulting from incomplete choroid fissure closure. Recently, the identification of individuals with coloboma in the superior aspect of the iris, retina, and lens led to the discovery of a novel structure, referred to as the superior fissure or superior ocular sulcus (SOS), that is transiently present on the dorsal aspect of the optic cup during vertebrate eye development. Although this structure is conserved across mice, chick, fish, and newt, our current understanding of the SOS is limited.

Morphogenetic defects underlie Superior Coloboma, a newly identified closure disorder of the dorsal eye.

The eye primordium arises as a lateral outgrowth of the forebrain, with a transient fissure on the inferior side of the optic cup providing an entry point for developing blood vessels. Incomplete closure of the inferior ocular fissure results in coloboma, a disease characterized by gaps in the inferior eye and recognized as a significant cause of pediatric blindness. Here, we identify eight patients with defects in tissues of the superior eye, a congenital disorder that we term superior coloboma.

Rare Enterorectal Pelvic Floor Hernia-A Cadaveric Study.

We present a cadaveric case study of an 88-year-old woman with an unusual posterior perineal hernia containing small bowel, rectum, and mesentery. Dissection revealed several loops of the small bowel occupying the presacral space and displacement of the rectum into a large perineal evagination. The intestinal mucosa appeared to have been healthy at the time of death, and we did not find any indication of rectal prolapse.

Zebrafish jam-b2 Gal4-enhancer trap line recapitulates endogenous jam-b2 expression in extraocular muscles.

Background: Members of the junctional adhesion molecule (JAM) family function as cell adhesion molecules and cell surface receptors. The zebrafish genome contains six different jam genes, and jam-b and jam-c were shown to be essential for myoblast fusion during skeletal muscle development. However, little is known about jam-b2 expression and function.

The role of Zic transcription factors in regulating hindbrain retinoic acid signaling.

Background: The reiterated architecture of cranial motor neurons aligns with the segmented structure of the embryonic vertebrate hindbrain. Anterior-posterior identity of cranial motor neurons depends, in part, on retinoic acid signaling levels. The early vertebrate embryo maintains a balance between retinoic acid synthetic and degradative zones on the basis of reciprocal expression domains of the retinoic acid synthesis gene aldhehyde dehydrogenase 1a2 (aldh1a2) posteriorly and the oxidative gene cytochrome p450 type 26a1 (cyp26a1) in the forebrain, midbrain, and anterior hindbrain.

Studying cellular and subcellular dynamics in the developing zebrafish nervous system.

Cells of the developing nervous system undergo incredible proliferation, migrate long distances, and differentiate morphologically into highly specialized structures. The dynamic changes happening at the cellular and subcellular levels can only be properly understood using time-lapse in vivo imaging approaches, for which the transparent embryonic zebrafish is ideally suited. Moreover, the genetic techniques adapted for zebrafish provide incredible spatial, temporal, and quantitative control over the expression of fluorescent proteins, such that practically any structure or cell of interest can be highlighted.

IAPs regulate the plasticity of cell migration by directly targeting Rac1 for degradation.

Inhibitors of apoptosis proteins (IAPs) are a highly conserved class of multifunctional proteins. Rac1 is a well-studied Rho GTPase that controls numerous basic cellular processes. While the regulation of nucleotide binding to Rac1 is well understood, the molecular mechanisms controlling Rac1 degradation are not known.

In vivo cell biology using Gal4-mediated multicolor subcellular labeling in zebrafish.

The behavior of a cell is determined by the interplay of its subcellular components. Thus, being able to simultaneously visualize several organelles inside cells within the natural context of a living organism could greatly enhance our understanding of developmental processes. We have established a Gal4-based system for the simultaneous and cell type specific expression of multiple subcellular labels in transparent zebrafish embryos.

The centrosome neither persistently leads migration nor determines the site of axonogenesis in migrating neurons in vivo.

The position of the centrosome ahead of the nucleus has been considered crucial for coordinating neuronal migration in most developmental situations. The proximity of the centrosome has also been correlated with the site of axonogenesis in certain differentiating neurons. Despite these positive correlations, accumulating experimental findings appear to negate a universal role of the centrosome in determining where an axon forms, or in leading the migration of neurons.

Distinct roles for Robo2 in the regulation of axon and dendrite growth by retinal ganglion cells.

Guidance factors act on the tip of a growing axon to direct it to its target. What role these molecules play, however, in the control of the dendrites that extend from that axon's cell body is poorly understood. Slits, through their Robo receptors, guide many types of axons, including those of retinal ganglion cells (RGCs).

LIMK1 acts downstream of BMP signaling in developing retinal ganglion cell axons but not dendrites.

The actin cytoskeleton inside extending axonal and dendritic processes must undergo continuous assembly and disassembly. Some extrinsic factors modulate actin turnover through controlling the activity of LIM kinase 1 (LIMK1), which phosphorylates and inactivates the actin depolymerizing factor cofilin. Here, we for the first time examine the function and regulation of LIMK1 in vivo in the vertebrate nervous system.

TGFbeta ligands promote the initiation of retinal ganglion cell dendrites in vitro and in vivo.

Each type of neuron develops a unique morphology critical to its function, but almost all start with the basic plan of one long axon and multiple short, branched dendrites. Though extrinsic signals are known to direct many steps in the development of neuronal structure, little is understood about the initiation of processes, particularly dendrites. We find that Xenopus retinal ganglion cells (RGCs) explanted early will extend axons and not dendrites in dissociated cultures.

Targeting of retinal axons requires the metalloproteinase ADAM10.

The role of extrinsic cues in guiding developing axons is well established; however, the means by which the activity of these extrinsic cues is regulated is poorly understood. A disintegrin and metalloproteinase (ADAM) enzymes are Zn-dependent proteinases that can cleave guidance cues or their receptors in vitro. Here, we identify the first example of a metalloproteinase that functions in vertebrate axon guidance in vivo.

Expression of Bmp ligands and receptors in the developing Xenopus retina.

Bone morphogenetic proteins (BMPs) act repeatedly in the development of nervous system tissues. While BMP signaling is critical for the early growth and patterning of the eye, we are interested in possible later functions of BMPs in the morphological development of retinal neurons and formation of synaptic connections. Therefore, we conducted an in situ hybridization analysis of the mRNA expression for the ligands Bmp2, -4 and 7 and the type Ia, Ib and II receptors (BmprIa, BmprIb and BmprII) during development of the retina of Xenopus laevis.

Zac1 promotes a Müller glial cell fate and interferes with retinal ganglion cell differentiation in Xenopus retina.

The timing of cell cycle exit is tightly linked to cell fate specification in the developing retina. Accordingly, several tumor suppressor genes, which are key regulators of cell cycle exit in cancer cells, play critical roles in retinogenesis. Here we investigated the role of Zac1, a tumor suppressor gene encoding a zinc finger transcription factor, in retinal development.

Matrix metalloproteinases are required for retinal ganglion cell axon guidance at select decision points.

Axons receive guidance information from extrinsic cues in their environment in order to reach their targets. In the frog Xenopus laevis, retinal ganglion cell (RGC) axons make three key guidance decisions en route through the brain. First, they cross to the contralateral side of the brain at the optic chiasm.