Uncovering the role of ankyrins in photoreceptor wiring
Ended Project Grant Awarded Last action
- Award ID
- F31EY035931
- Recipient
-
Baylor College Of Medicine UEI FXKMA43NTV21
- Awarding agency
-
National Eye Institute
National Institutes of Health, Department of Health and Human Services
- Obligated
- $142,556
Award facts
- Assistance listing
- 93.867 Vision Research
- Completion date
- Place of performance
- Texas, USA
Award details come from USAspending.gov.
Description
- Abstract
- Proper synaptic connectivity between photoreceptors and their respective partners is essential for normal visual transmission and processing. The inability of photoreceptors to form synaptic connections during development underlies many vision-related neurodevelopmental disorders. Thus, elucidating the developmental mechanisms that mediate appropriate photoreceptor connectivity will provide insights into devising therapeutic approaches to treat patients with retinal diseases. In the mammalian retina, the different types of photoreceptors synapse selectively to distinct postsynaptic targets: horizontal cells and bipolar neurons. During development, photoreceptors first make contacts to horizontal cells (referred to as first synaptic contact) and then to bipolar neurons (i.e. second synaptic contact). Although the timing and patterns of connections have been well- described for photoreceptors, little is known about the early molecular events that coordinate the selective wiring of photoreceptors to their respective targets. In this proposal, we investigate a new role for the cytoskeletal scaffolding proteins, ankyrins in mediating the early developmental events involved in photoreceptor connectivity. In my preliminary data, I found ankyrin-B (ANKB) and ankyrin-G (ANKG) to be differentially expressed in both a spatial and temporal manner in the developing retina. ANKB is highly expressed in horizontal cells at early time points when the first synaptic connection between photoreceptors and horizontal cells is being established, whereas ANKG is expressed at later stages in bipolar neurons when the second synaptic connection is formed. Moreover, my initial data reveals that loss of ANKB and ANKG results in phenotypes consistent with synaptic connectivity defects between photoreceptors and their synaptic targets. Additionally, I also find that there are impaired retinal responses in animals with disruption of ANKB and ANKG compared to controls. Therefore, I hypothesize that ankyrins are the key molecules that mediate selective wiring of photoreceptors to their postsynaptic partners during development. To test my hypothesis, I will utilize mouse transgenics, high-resolution imaging, and functional visual assays to identify the function of ankyrins in photoreceptor connectivity. Specifically, the proposed work will uncover the different roles of ankyrins in the cone and rod pathway (aim 1), the developmental mechanism of when ankyrins are required for synaptic connectivity (aim 2), and the cell-type specific requirements of ankyrins in photoreceptor connectivity (aim 3). By performing the proposed experiments, we will elucidate a new role for ankyrins in mediating synaptic connectivity in the developing retina. This work will have broad significance as IT may reveal new potential targets that can be used to restore photoreceptor connections in patients suffering from vision loss.
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | -$4,366 | |
| Amendment | $0 | |
| Amendment | $48,974 | |
| Amendment | $48,974 | |
| Amendment | $0 | |
| Amendment | $48,974 | |
| Original award | $0 |
Quick answers
Who received award F31EY035931?
F31EY035931 was awarded to Baylor College Of Medicine by National Eye Institute (National Institutes of Health) on April 17, 2025.
How much is award F31EY035931 worth?
$142,556 has been obligated on F31EY035931.
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