E A Schmitt

Harvard University, Cambridge, MA, United States

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Publications (6)42.87 Total impact

  • EA Schmitt, J E Dowling
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    ABSTRACT: The morphological differentiation of the zebrafish retina was analyzed by using light (LM) and transmission electron (TEM) microscopy between the time of initial ganglion cell differentiation (approximately 32 hours postfertilization; hpf) and shortly after the point when the retina appears functional (approximately 74 hpf), i.e., when all major cell types and basic synaptic connections are in place. The results show that the inner retinal neurons, like the photoreceptor and ganglion cells, differentiate first within the ventronasal region, and differentiation subsequently spreads asymmetrically into the nasal and dorsal regions before reaching the ventrotemporal retina. In addition, we show that the attenuation of the optic stalk occurs in parallel with ganglion cell differentiation between 32 and 40 hpf. The first conventional synapses appear within the inner plexiform layer simultaneously with the first photoreceptor outer segment discs at 60 hpf; functional ribbon triads arise within photoreceptor synaptic terminals at 65 hpf; and synaptic ribbons occur within bipolar cell axon terminals at the time larvae exhibit their first visual responses (approximately 70 hpf). Although development is initially more advanced within the ventronasal region between 50 and 60 hpf, development across the retina rapidly equilibrates such that it is relatively comparable within all quadrants of the central retina by 70 hpf. An area within the temporal retina characterized by tightly packed and highly tiered cones emerges with subsequent development. Retinal differentiation in the zebrafish corresponds with that generally described in other vertebrates and can be correlated with the development of visual and electroretinographic responses in the animal.
    The Journal of Comparative Neurology 03/1999; 404(4):515-36. · 3.51 Impact Factor
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    ABSTRACT: Application of exogenous retinoic acid (RA) to zebrafish during the initial stages of photoreceptor differentiation results in a precocious development of rod photoreceptors and an inhibition of cone photoreceptor maturation. The acceleration of rod differentiation is observed initially within the ventral retina 3 days after fertilization, following 24 hr of RA application, and within the dorsal retina 4 days after fertilization, following 48 hr of RA application. The differentiation of rods was impeded significantly when the synthesis of endogenous retinoic acid was inhibited by citral prior to the initial stage of rod differentiation. RA-treated embryos labeled for bromodeoxyuridine (BrdU) uptake revealed that RA exerts its effect on a postmitotic cell population within the developing retina. During normal development in zebrafish, rod differentiation is most robust within the ventral retina, a region previously shown to be rich in RA. Our data suggest that the RA signaling pathway is involved in the differentiation and maturation of both the rod and cone photoreceptors within the developing zebrafish retina.
    Proceedings of the National Academy of Sciences 12/1996; 93(23):13298-303. DOI:10.1073/pnas.93.23.13298 · 9.81 Impact Factor
  • E A Schmitt, J M Fadool, J E Dowling
    Investigative Ophthalmology &amp Visual Science 05/1996; 37(5):695. · 3.66 Impact Factor
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    ABSTRACT: The developing eye is known to be rich in retinoic acid (RA), and perturbations in RA levels during formation of the optic primordia, as well as RA receptor mutations, cause retinal malformations, especially in ventral eye regions. To test the hypothesis that RA plays a role in the establishment of ventral retinal characteristics, we examined several dorsal and ventral ocular markers in RA-treated zebrafish. The optic stalk represents the ventral-most region of the early eye field. During normal development, the optic stalks constrict, decreasing in width and are gradually replaced by the optic nerve. Systemic high RA levels cause an expansion in the optic stalk with an increased cell content and a patent lumen. In addition, the stalks do not constrict and persist into later stages of development indicating an enhancement of early ventral eye characteristics. Expression of the transcription factor pax[b], normally confined to the ventral retina, expands into the dorsal retina following RA treatment, whereas msh[c], normally expressed in the dorsal retinal pole, disappears. Activity of an aldehyde dehydrogenase that normally occupies the dorsal third of the retina is reduced or abolished following high systemic RA. When a localized RA source, an RA-soaked bead, is placed next to the developing eye, a fissure resembling the choroid fissure appears in the eye facing the bead. Taken together, these observations suggest that RA is involved in the determination of the ventral retina.
    Development 02/1996; 122(1):195-204. · 6.27 Impact Factor
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    ABSTRACT: In many vertebrates, UV-sensitive photoreceptors have been identified by microspectrophotometry and UV-visual sensitivity has been identified by behavioral studies, but as yet no vertebrate UV-sensitive pigment gene has been isolated. We have sequenced a cDNA clone that hybridizes to short single cone cells in the zebrafish (Brachydanio rerio). These cells, which make up 25% of the cone population in zebrafish retinae, are UV-sensitive (lambda max approximately 360 nm). The visual pigment encoded by this gene is unusual in that its amino acid sequence is more homologous to the rod pigment rhodopsin (up to 89%) than to other cone pigments (35-83%). Like all other vertebrate visual pigments, it contains a lysine residue at position 296, the presumptive retinal binding site, and a glutamate residue at position 113. However, it is unique in possessing a lysine residue at position 126, which may account for the UV-sensitivity of the pigment.
    Proceedings of the National Academy of Sciences 08/1993; 90(13):6009-12. DOI:10.1073/pnas.90.13.6009 · 9.81 Impact Factor
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    ABSTRACT: Exogenous treatment of zebrafish embryos with retinoic acid induces a duplication of the retinas during development. These effects occur only when retinoic acid is applied within a 2-hr period prior to and during the initial formation of the optic primordia, and they are concentration-dependent. Light microscopic examination reveals that the second retina derives from cells in the ventral region of the developing eyecup that normally become pigment epithelial cells. Two distinct ganglion cell fields are usually observed in eyes with duplicated retinas. Bundles of axons from each ganglion cell field join as they leave the eye and innervate the contralateral tectum.
    Proceedings of the National Academy of Sciences 10/1992; 89(17):8293-7. DOI:10.1073/pnas.89.17.8293 · 9.81 Impact Factor