Summary The transcription factor NRL (neural retina leucine zipper) has been canonized as the master regulator of photoreceptor cell fate in the retina. NRL is necessary and sufficient to specify rod cell fate and to preclude cone cell fate in mice. By engineering zebrafish, we tested if NRL function has conserved roles beyond mammals or beyond nocturnal species, i.e., in a vertebrate possessing a greater and more typical diversity of cone sub-types. Transgenic expression of Nrl from zebrafish or mouse was sufficient to induce rod photoreceptor cells. Zebrafish nrl −/− mutants lacked rods (and had excess UV-sensitive cones) as young larvae; thus, the conservation of Nrl function between mice and zebrafish appears sound. Strikingly, however, rods were abundant in adult nrl −/− null mutant zebrafish. Rods developed in adults despite Nrl protein being undetectable. Therefore, a yet-to-be-revealed non-canonical pathway independent of Nrl is able to specify the fate of some rod photoreceptors.
Cryptochromes (CRY) are highly conserved signalling molecules that regulate circadian rhythms and are candidate radical pair based magnetoreceptors. Birds have at least four cryptochromes (CRY1a, CRY1b, CRY2, and CRY4), but few studies have interrogated their function. Here we investigate the expression, localisation and interactome of clCRY2 in the pigeon retina. We report that clCRY2 has two distinct transcript variants, clCRY2a, and a previously unreported splice isoform, clCRY2b which is larger in size. We show that clCRY2a mRNA is expressed in all retinal layers and clCRY2b is enriched in the inner and outer nuclear layer. To define the localisation and interaction network of clCRY2 we generated and validated a monoclonal antibody that detects both clCRY2 isoforms. Immunohistochemical studies revealed that clCRY2a/b is present in all retinal layers and is enriched in the outer limiting membrane and outer plexiform layer. Proteomic analysis showed clCRY2a/b interacts with typical circadian molecules (PER2, CLOCK, ARTNL), cell junction proteins (CTNNA1, CTNNA2) and components associated with the microtubule motor dynein (DYNC1LI2, DCTN1, DCTN2, DCTN3) within the retina. Collectively these data show that clCRY2 is a component of the avian circadian clock and unexpectedly associates with the microtubule cytoskeleton.
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. RESULTS. Although rod and cone photoreceptors differentiate in gdf6a mutant zebrafish, the cells display aberrant growth and morphology. The cone outer segments, the lightdetecting sensory endings, are reduced in size in the mutant larvae and fail to recover to control size at subsequent stages. In contrast, rods form temporarily expanded outer segments. The inner segments, which generate the required energy and proteins for the outer segments, are shortened in both rods and cones at all stages. RNA-Seq analysis provides a set of misregulated genes associated with the observed abnormal photoreceptor morphogenesis. CONCLUSIONS. GDF6 mutations were previously identified in patients with Leber congenital amaurosis. Here, we reveal a unique photoreceptor phenotype in the gdf6a mutant zebrafish whereby rods and cones undergo abnormal maturation distinct for each cell type. Further, subsequent development shows partial recovery of cell morphology and maintenance of the photoreceptor layer. By conducting a transcriptomic analysis of the gdf6a larval eyes, we identified a collection of genes that are candidate regulators of photoreceptor size and morphology.
Highlights-Nrl is conserved and sufficient to specify rod photoreceptors in zebrafish retina -Nrl is necessary for rod photoreceptors in early ontogeny of zebrafish larvae -Zebrafish Nrl is functionally conserved with mouse and human NRL -Remarkably, Nrl is dispensable for rod specification in adult zebrafish Abstract 1The transcription factor NRL (Neural Retinal Leucine-zipper) has been canonized, 2 appropriately enough, as the master regulator of photoreceptor cell fate in the retina. NRL 3 is necessary and sufficient to specify rod cell fate and to preclude cone cell fate in mice. 4By engineering zebrafish we tested if NRL function has conserved roles beyond mammals 5 or beyond nocturnal species, i.e. in a vertebrate possessing a greater and more typical 6 diversity of cone sub-types. Here, transgenic expression of a Nrl homolog from zebrafish 7 or mouse was sufficient to convert developing zebrafish cones into rod photoreceptors. 8Zebrafish nrl -/mutants lacked rods (and had excess UV-sensitive cones) as young larvae, 9thus the conservation of Nrl function between mice and zebrafish appears sound. These 10 data inform hypotheses of photoreceptor evolution through the Nocturnal Bottleneck, 11suggesting that a capacity to favor nocturnal vision is a property of NRL that predates the 12 emergence of early mammals. Strikingly, however, rods were abundant in adult nrl -/null 13 mutant zebrafish. Rods developed in adults despite Nrl protein being undetectable. 14 Therefore a yet-to-be-revealed non-canonical pathway independent of nrl is able to specify 15 the fate of some rod photoreceptors. 16 17 Keywords 18Nocturnal Bottleneck; Gene Regulatory Network; Visual system development; Evo-Devo; 20Rods and cones are the ciliary photoreceptors used by vertebrates to enable vision 21 across a broad range of circumstances. Rod photoreceptors enable vision in dim 22conditions, while cone photoreceptors convey wavelength-specific information, enable 23high acuity and can operate in brightly lit environments. Retinas with both rods and cones 24 are known as duplex retinas, and the basic features of the duplex retina are present even 25 among some of the earliest branching vertebrates, the lampreys [1-3]. 26The visual photoreceptors are among the best-studied neurons with respect to 27 developmental programs and gene regulatory networks. Photoreceptor precursor cells of 28 the developing mouse retina are thoroughly studied, and an elegantly simple gene 29 regulatory network determines all rod and cone cell fates. As the precursor cell exits its 30terminal mitosis, expression of the bZIP transcription factor NRL directs it to a rod fate 31(schematized in Fig. 1A); without NRL expression it develops as a cone [4][5][6][7]. With high 32 activity of the thyroid hormone receptor THRB, the presumptive cone will develop into the 33 medium (green) wavelength light-sensitive M-cone (the ancestral red cone, expressing 34 LWS opsin). Without THRB activity, it becomes a short wavelength (UV/blue) light-35 sensitive S-cone (the ancestral U...
New neurons continuously arise from neural progenitor cells in the dentate gyrus of the adult hippocampus to support ongoing learning and memory formation. To generate functional adult-born neurons, neural progenitor cells proliferate to expand the precursor cell pool and differentiate into neurons. Newly generated cells then undergo postmitotic maturation to migrate to their final destination and develop elaborate dendritic branching, which allows them to receive input signals. Little is known about factors that regulate neuronal differentiation, migration, and dendrite maturation during adult hippocampal neurogenesis. Here, we show that the transcriptional repressor protein capicua (CIC) exhibits dynamic expression in the adult dentate gyrus. Conditional deletion of Cic from the mouse dentate gyrus compromises the adult neural progenitor cell pool without altering their proliferative potential. We further demonstrate that the loss of Cic impedes neuronal lineage development and disrupts dendritic arborization and migration of adult-born neurons. Our study uncovers a previously unrecognized role of CIC in neurogenesis of the adult dentate gyrus.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.