Doç. Dr. Arzu ÇELIK
Moleküler Biyoloji ve Genetik Bölümü
Kuzey Park, 302
34342 Bebek - Istanbul
+90 (212) 359 7562
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Cell Type Specification During Eye Development
A fundamental problem common to the development of most sensory systems is the generation of functionally distinct neuronal cell types. The visual system constitutes a unique model to study the generation of cellular diversity within an otherwise homogeneous neuronal population. We use the fly retina to dissect signaling events that regulate the late phase of eye development, in particular those that control the selective expression of different rhodopsin genes in distinct photoreceptor (PR) subtypes. In many cases it has been shown that factors important for the development of the fly retina may also play a role in the vertebrate retina. Thus, in addition to the elucidation of basic developmental processes, our studies will aid the development of tools to fight eye diseases in humans.
In Drosophila color vision is achieved by the differential expression of blue-, green-, and uv-sensitive rhodopsin molecules in R7 and R8 cells. Throughout the retina, color ommatidia fall into two classes, pale and yellow that are defined by the expression of different sets of rhodopsin molecules in the inner PR cells R7 and R8. Pale and yellow ommatidia are distributed randomly in the fly retina with a ratio of 30:70 and results from a stochastic decision in R7 cells, which is then communicated to the underlying R8 cell.
While the genetic pathways regulating the initial steps of the differentiation of inner PRs have been understood in some detail later steps of PR differentiation are widely unknown. We could show that the specification of the yellow ommatidial subtype is induced by the bHLH transcription factor spineless, whereas ommatidia expressing the transcription factor orthodenticle adopt the pale fate. However, the signaling pathway that activates the specific rhodopsin in yellow R7 cells is still not known. Additionally, the molecules and pathways that underlie signaling between R7 and R8 cells, which are responsible for the correlated expression of specific pairs of rhodopsins in pale and yellow ommatidia remain equally elusive. Aiming to identify missing members of this differentiation pathway we have previously performed a genetic screen using enhancer trapping. We will determine the roles of this newly identified genes in late stages of PR differentiation and rhodopsin expression.
Sensory Receptor Exclusion in the Olfactory System of Flies
A common phenomenon in sensory systems is the expression of one sensory receptor per sensory neuron. However, the mechanisms underlying this phenomenon are largely unknown. The maxillary palp of Drosophila melanogaster presents a unique model to study mechanisms of sensory receptor exclusion. We are currently investigating the role of the transcription factors of the iroC family for their involvement in this process.
Role of Glial Cells in Circuit Formation
The development of the nervous system requires that neurons find their correct targets and establish specific synaptic connections with their partners. Glial cells are important in the development and maintenance of the nervous system. They provide neuronal trophic support, help with axon pathfinding and nerve fasciculation, and are involved in the clearance of dead cells from the CNS.
The olfactory system of Drosophila represents an interesting example of how a large repertoire of neuron types are specified and assembled into functional circuits. The question of how a precise olfactory map can be established is of major interest.
We have identified a novel cell adhesion molecule involved in the guidance of olfactory sensory neurons that is mainly expressed by glial cells. This study has led us to the investigation of a glial cell population known as the transient interhemispheric fibrous ring and its role in olfactory circuit formation.
Generation of Disease Models in Flies
- Şahin HB, Sayın S, Holder M, Buğra K, and Çelik A (2020) Salt Inducible Kinases as Novel Notch Interactors in the Developing Drosophila Retina. PLoS One, 15(6): e0234744
- Terzioğlu Kara E, Kıral FR, Öztürk Çolak A, and Çelik A (2020) Generation and characterization of inner photoreceptor‐specific enhancer‐trap lines using a novel piggyBac‐Gal4 element in Drosophila. Archives of Insect Biochemistry and Physiology, 104(2):e21675
- Kazeminasab S, Taşkıran II, Fattahi Z, Bazzazzadegan N, Hosseini M, Rahimi M, Olaad Nabi M, Haddadi M, Çelik A, Ropers HH, Najmabadi H, and K Kahrizi K (2018) CNKSR1 gene defect can cause syndromic autosomal recessive intellectual disability. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics 177(8):691-699. doi: 10.1002/ajmg.b.32648
- Fattahi Z, Sheikh T, Musante L, Rasheed M, Taşkıran II, Harripaul R, Hu H, Kazeminasab S, Alam MR, Hosseini M, Larti F, Ghaderi Z, Çelik A, Ayub M, Ansar M, Haddadi M, Wienker TF, Ropers HH, Kahrizi K, Vincent JB, and H Najmabadi (2018) Biallelic missense variants in ZBTB11 can cause intellectual disability in human. Human Molecular Genetics 27(18):3177-3188. doi: 10.1093/hmg/ddy220.
- Köstler S, Alaybeyoğlu B, Weichenberger CX, and Çelik A (2015) FlyOde – a platform for community curation and interactive visualization of dynamic gene regulatory networks in Drosophila eye development. F1000 Research 4:1484-9.
- Potier D, Davie K, Hulselmans G, Sanchez MN, Haagen L, Huynh-Thu VA, Koldere D, Çelik A, Geurts P, Christiaens V, and Aerts S (2014) Mapping gene regulatory networks in Drosophila eye development by large-scale transcriptome perturbations and motif inference. Cell Reports 9:1-14.
- Tsachaki M, Mishra AK, Rister J, Ng J, Çelik A, and Sprecher SG (2013) Binary cell fate decisions and fate transformation in the Drosophila larval eye. PLoS Genetics 9(12):e1004027.
- Li X, Erclik T, Chen Z, Venkatesh S, Morante J, Çelik A, and Desplan C, (2013) Temporal specification of neuroblasts controls neuronal diversity in the Drosophila medulla. Nature 498(7455):456-62.
- Vasiliauskas D, Mazzoni EO, Sprecher SG, Johnston RJ Jr, Lidder P, Vogt N, Çelik A, and Desplan C (2011) Feedback from Rhodopsin controls Rhodopsin exclusion in Drosophila R8 photoreceptors. Nature 479(7371):108-12.
- Mazzoni EO, Çelik A, Wernet MF, Vasiliauskas D, Cook TA, Johnston RJ, Pichaud F, and Desplan C (2008) Iroquois-Complex genes induce co-expression of visual pigments in Drosophila. PLoS Biology 6(4):e9.
- Wernet MF, Çelik A, Mikeladze-Dvali T, and Desplan C (2007) Generation of uniform fly retinas. Current Biology 17(23):r1002-3.