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Genetic and Molecular Mechanisms Controlling Photoreceptor Development

English title Genetic and Molecular Mechanisms Controlling Photoreceptor Development
Applicant Sprecher Simon
Number 169993
Funding scheme Project funding (Div. I-III)
Research institution Département de Biologie Faculté des Sciences Université de Fribourg
Institution of higher education University of Fribourg - FR
Main discipline Embryology, Developmental Biology
Start/End 01.10.2016 - 30.09.2019
Approved amount 618'702.00
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All Disciplines (4)

Discipline
Embryology, Developmental Biology
Zoology
Genetics
Molecular Biology

Keywords (5)

Drosophila; Cell fate idendity; Neuronal development; Photoreceptor neurons; Transcription factor

Lay Summary (German)

Lead
Genetische Kontrolle der Entwicklung von Photorezeptorzellen
Lay summary
Die Fähigkeit zu sehen ist von der Funktion der Augen abhängig. Die Zellen des Auges, welche Licht in neuronale Signale umwandeln sind die Photorezeptorzellen. Die Gene welche verantwortlich sind für die Augenentwicklung in einem frühen Stadium während der Entwicklung sind bekannt. Allerdings weiss man nicht wie diese frühen Prozesse es einer neuronalen Stammzelle erlaubt sich in eine Photorezeptorzellen zu entwickeln. Wir haben gezeigt, dass der Transkriptionsfaktor “Glass“ eine wichtige Rolle in diesem Prozess spielt. In diesem Projekt studieren wir die genetischen und molekularen Mechanismen wie Glass zusammen mit andern Genen die Idendität von Photorezeptorzellen determiniert. 
 
Direct link to Lay Summary Last update: 06.10.2016

Responsible applicant and co-applicants

Employees

Publications

Publication
Multilevel regulation of the glass locus during Drosophila eye development
Fritsch Cornelia, Bernardo-Garcia F. Javier, Humberg Tim-Henning, Mishra Abhishek Kumar, Miellet Sara, Almeida Silvia, Frochaux Michael V., Deplancke Bart, Huber Armin, Sprecher Simon G. (2019), Multilevel regulation of the glass locus during Drosophila eye development, in {PLOS} Genetics, 15(7), 1008269-1008269.
Muscarinic acetylcholine receptor signaling generates OFF selectivity in a simple visual circuit
Qin Bo, Humberg Tim-Henning, Kim Anna, Kim Hyong S., Short Jacob, Diao Fengqiu, White Benjamin H., Sprecher Simon G., Yuan Quan (2019), Muscarinic acetylcholine receptor signaling generates OFF selectivity in a simple visual circuit, in Nature Communications, 1.
An expression atlas of variant ionotropic glutamate receptors identifies a molecular basis of carbonation sensing
Sánchez-Alcañiz Juan Antonio, Silbering Ana Florencia, Croset Vincent, Zappia Giovanna, Sivasubramaniam Anantha Krishna, Abuin Liliane, Sahai Saumya Yashmohini, Münch Daniel, Steck Kathrin, Auer Thomas O., Cruchet Steeve, Neagu-Maier G. Larisa, Sprecher Simon G., Ribeiro Carlos, Yapici Nilay, Benton Richard (2018), An expression atlas of variant ionotropic glutamate receptors identifies a molecular basis of carbonation sensing, in Nature Communications, 9(1), 4252-4252.
Two Pairs of Drosophila Central Brain Neurons Mediate Larval Navigational Strategies Based on Temporal Light Information Processing
Humberg Tim-Henning, Sprecher Simon G. (2018), Two Pairs of Drosophila Central Brain Neurons Mediate Larval Navigational Strategies Based on Temporal Light Information Processing, in Frontiers in Behavioral Neuroscience, 12, 1.
Multiple neurons encode CrebB dependent appetitive long-term memory in the mushroom body circuit
Widmer Yves F, Fritsch Cornelia, Jungo Magali M, Almeida Silvia, Egger Boris, Sprecher Simon G (2018), Multiple neurons encode CrebB dependent appetitive long-term memory in the mushroom body circuit, in eLife, 7, 1.
Xenacoelomorpha Survey Reveals That All 11 Animal Homeobox Gene Classes Were Present in the First Bilaterians
Brauchle Michael, Bilican Adem, Eyer Claudia, Bailly Xavier, Martínez Pedro, Ladurner Peter, Bruggmann Rémy, Sprecher Simon G (2018), Xenacoelomorpha Survey Reveals That All 11 Animal Homeobox Gene Classes Were Present in the First Bilaterians, in Genome Biology and Evolution, 10(9), 2205-2217.
Patterning mechanisms diversify neuroepithelial domains in the Drosophila optic placode
Mishra Abhishek Kumar, Bernardo-Garcia F. Javier, Fritsch Cornelia, Humberg Tim-Henning, Egger Boris, Sprecher Simon G. (2018), Patterning mechanisms diversify neuroepithelial domains in the Drosophila optic placode, in PLOS Genetics, 14(4), e1007353-e1007353.
Dedicated photoreceptor pathways in Drosophila larvae mediate navigation by processing either spatial or temporal cues
Humberg Tim-Henning, Bruegger Pascal, Afonso Bruno, Zlatic Marta, Truman James W., Gershow Marc, Samuel Aravinthan, Sprecher Simon G. (2018), Dedicated photoreceptor pathways in Drosophila larvae mediate navigation by processing either spatial or temporal cues, in Nature Communications, 9(1), 1.
Organization of the Drosophila larval visual circuit
Larderet Ivan, Fritsch Pauline MJ, Gendre Nanae, Neagu-Maier G Larisa, Fetter Richard D, Schneider-Mizell Casey M, Truman James W, Zlatic Marta, Cardona Albert, Sprecher Simon G (2017), Organization of the Drosophila larval visual circuit, in eLife, 6, 1.
Age- and Wavelength-Dependency of Drosophila Larval Phototaxis and Behavioral Responses to Natural Lighting Conditions
Humberg Tim-Henning, Sprecher Simon G. (2017), Age- and Wavelength-Dependency of Drosophila Larval Phototaxis and Behavioral Responses to Natural Lighting Conditions, in Frontiers in Behavioral Neuroscience, 11, 1.
Successive requirement of Glass and Hazy for photoreceptor specification and maintenance in Drosophila
Bernardo-Garcia F. Javier, Humberg Tim-Henning, Fritsch Cornelia, Sprecher Simon G. (2016), Successive requirement of Glass and Hazy for photoreceptor specification and maintenance in Drosophila, in Fly, 11(2), 112-120.
A microfluidics-based method for measuring neuronal activity in Drosophila chemosensory neurons
van Giesen Lena, Neagu-Maier G Larisa, Kwon Jae Young, Sprecher Simon G (2016), A microfluidics-based method for measuring neuronal activity in Drosophila chemosensory neurons, in Nature Protocols, 11(12), 2389-2400.
The transcription factor Glass links eye field specification with photoreceptor differentiation in Drosophila
Bernardo-Garcia F. Javier, Fritsch Cornelia, Sprecher Simon G. (2016), The transcription factor Glass links eye field specification with photoreceptor differentiation in Drosophila, in Development, 143(8), 1413-1423.
Functional genomics identifies regulators of the phototransduction machinery in the Drosophila larval eye and adult ocelli.
Mishra AK, Bargmann BO, Tsachaki M, Fritsch C, Sprecher SG (2016), Functional genomics identifies regulators of the phototransduction machinery in the Drosophila larval eye and adult ocelli., in Developmental Biology, 1.

Associated projects

Number Title Start Funding scheme
189785 Multichannel confocal microscope with fluorescence lifetime imaging for life science samples 01.03.2020 R'EQUIP
149499 Characterizing the genetic network mediating the binary cell fate decision in the Drosophila larval eye 01.10.2013 Project funding (Div. I-III)
183379 A GC/Q-TOF for selective detection and accurate identification of key metabolites involved in biological and geological processes 01.12.2018 R'EQUIP
188471 Mechanisms Controlling Chemosensory Cell Type Diversity in Drosophila 01.10.2019 Project funding (Div. I-III)

Abstract

Specialized sensory organs allow us to perceive the surrounding world. Each senseorgan harbors defined types of sensory neurons, which house the biochemical machineries able to translate physical cues (such as light, temperature or pressure) or chemical cues (such as odorants or tastants) into intracellular molecular signals. For the sense of vision our eyes contain photoreceptor neurons (PRs), which express light-sensitive G-protein coupled receptors (GPCRs), which are termed Opsin/Rhodopsins. Upon the activation of Opsin/Rhodopsin by a photon the associated trimeric G-proteins initiate a molecular cascade, which ultimately will result in the hyperpolarization or depolarization of the membrane potential. The presence of these phototransduction cascade and the Opsin/Rhodopsins proteins is a key feature of PRs. While the molecular function of phototransduction cascade has been well studied, much less is known regarding the developmental pathways that allow the differentiation of a precursor cell into a functional PR and the expression of the phototransduction cascade. Development of the eye is dependent on an evolutionarily conserved network of transcription factors termed Retinal Determination Network (RDN). Genes of the RDN are both necessary and sufficient for the formation of eye tissue. The molecular and genetic functions have been studied in great detail using the fruit fly Drosophila melanogaster as model system. However the genetic and molecular mechanisms of how the RDN acts to promote photoreceptor precursors to develop into mature PRs as compared to an alternative neuronal cell fate remains unknown. We have recently shown that the zinc finger transcription factor Glass provides an important link between the RDN and PR terminal differentiation. In glass mutants PR precursors adopt a neuronal identity, but fail to express virtually all tested markers of a mature PR identity. Glass expression is regulated by the RDN gene sine oculis suggesting that glass is genetically downstream of the RDN. Moreover Glass acts directly on the enhancers of the homeodomain transcription factor Hazy to promote its expression. Hazy has previously been identified as important player in PR terminal differentiation. Interestingly severl developmental defects found in glass mutants can be restored by expressing Hazy. However Hazy is not fully capable of rescuing the glass mutant phenotype suggesting that also other downstream transcription factors are required for terminal differentiation and/or that Glass directly regulates terminal differentiation. Moreover while Glass can induce the expression of some phototransduction genes in other neuronal tissues it appears by itself not to be sufficient to let any neuronal precursor develop into a PR. Thus we aim here to unveil molecular and genetic mechanisms of how early eye field specification in conjunction with transcription factors (such as Glass or Hazy) coordinates neuronal precursors to differentiate into fully functioning PRs.
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