Ossicle Development in the Chicken Cornea under the effect of Chemotherapy Drug DON

Major

Neuroscience

Submission Type

Poster

Area of Study or Work

Biology, Neuroscience

Faculty Advisor

Tyler Schwend

Location

CNS Atrium

Start Date

4-12-2025 8:30 AM

End Date

4-12-2025 9:30 AM

Abstract

Scleral ossicles, a concentric ring of 13-15 trapezoid-shaped flat bones that surround the cornea and provide structural support to the eye, are directly induced to form upon reception of molecular signals secreted by transient thickenings in the overlying conjunctival epithelium known as conjunctival papillae. Papillae induction is highly coordinated in both space and time. The full ring of 13-15 papillae arise within a distinctive pattern involving successive stages of 3-4 papillae arising at precise locations within the eye over 1.5 days of development, from embryonic day (E)6.5-8. Specifically, the first group of 3-4 papillae arise in the temporal quadrant of the eye, the second group arise later in the nasal quadrant of the eye, the third group form shortly thereafter in the dorsal quadrant before the last group arise in the ventral quadrant. Despite this, papillae development is not well understood. This study establishes a novel experimental paradigm for studying papillae induction that involves chick embryos exposed to the chemotherapy drug 6-diazo-5-oxo-l- norleucine (DON). Specifically, embryonic exposure with DON prior to the onset of papillae induction at E6 can fully and completely block papillae formation, and consequently scleral ossicle induction, in a dose-dependent fashion. Strikingly, by modulating the timing of DON exposure within the 1.5 day developmental window we found that papillae arising prior to DON treatment formed normally, while those not yet induced at the time of treatment failed to form. Collectively, these findings strongly support the notion that DON blocks the production and/or reception of the papillae induction signal. Gene expression analysis is currently underway and aims to identify candidate genes with known function in placode/papillae development (e.g. in feather and taste bud formation) that are either upregulated or downregulated in the DON treated eyes compared to control. These studies will pave the way for finding the source, identity and nature of molecules necessary for papillae development.

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Apr 12th, 8:30 AM Apr 12th, 9:30 AM

Ossicle Development in the Chicken Cornea under the effect of Chemotherapy Drug DON

CNS Atrium

Scleral ossicles, a concentric ring of 13-15 trapezoid-shaped flat bones that surround the cornea and provide structural support to the eye, are directly induced to form upon reception of molecular signals secreted by transient thickenings in the overlying conjunctival epithelium known as conjunctival papillae. Papillae induction is highly coordinated in both space and time. The full ring of 13-15 papillae arise within a distinctive pattern involving successive stages of 3-4 papillae arising at precise locations within the eye over 1.5 days of development, from embryonic day (E)6.5-8. Specifically, the first group of 3-4 papillae arise in the temporal quadrant of the eye, the second group arise later in the nasal quadrant of the eye, the third group form shortly thereafter in the dorsal quadrant before the last group arise in the ventral quadrant. Despite this, papillae development is not well understood. This study establishes a novel experimental paradigm for studying papillae induction that involves chick embryos exposed to the chemotherapy drug 6-diazo-5-oxo-l- norleucine (DON). Specifically, embryonic exposure with DON prior to the onset of papillae induction at E6 can fully and completely block papillae formation, and consequently scleral ossicle induction, in a dose-dependent fashion. Strikingly, by modulating the timing of DON exposure within the 1.5 day developmental window we found that papillae arising prior to DON treatment formed normally, while those not yet induced at the time of treatment failed to form. Collectively, these findings strongly support the notion that DON blocks the production and/or reception of the papillae induction signal. Gene expression analysis is currently underway and aims to identify candidate genes with known function in placode/papillae development (e.g. in feather and taste bud formation) that are either upregulated or downregulated in the DON treated eyes compared to control. These studies will pave the way for finding the source, identity and nature of molecules necessary for papillae development.