"Production and maintenance of proper neuron numbers in the developing " by Adelyn R. Carney, Cory Meyers et al.
 

Level of Education of Students Involved

Undergraduate

Faculty Sponsor

Masaru Nakamoto

College

College of Arts & Sciences (CAS)

Discipline(s)

Biology

Presentation Type

Poster Presentation

Symposium Date

Spring 4-24-2025

Abstract

Nervous system functionality depends on the generation and maintenance of the proper numbers of neurons. However, the molecular mechanisms that control the number of neurons produced during development and support long term neuronal survival are not fully understood. Nell2 is a multi-modular extracellular glycoprotein predominantly expressed in the nervous system. Nell2 exerts diverse functions in neural development, including regulation of neuronal proliferation and differentiation, and neuronal network formation. Our previous study has shown that Nell2 acts as an inhibitory guidance cue for retinal axons in the eye-specific visual (retinogeniculate) projection. In this study, we investigated the function of Nell2 in neuronal survival by using chick in ovo electroporation and Nell2 knockout mice. Nell2 is strongly expressed in retinal ganglion cells (RGCs) of chick embryos and in mice. Overexpression of Nell2 in the developing chick retina significantly increased RGC numbers, whereas Nell2 knockdown reduced them. Nell2 did not significantly affect neuronal proliferation. However, Nell2 promoted survival of RGCs in the developing retina by preventing apoptosis. In Nell2 knockout mice, the numbers of RGC significantly decreased in the developing retina, due to increased apoptosis. A continuous decrease in RGC numbers and increase in apoptotic RGCs were found in the aging Nell2 knockout mice. Furthermore, we detected Ros1 expression, a receptor tyrosine kinase that binds to Nell2, in RGCs by immunohistochemistry. These results suggest that Nell2 acts as a survival promoting factor essential for production and maintenance of proper numbers of RGCs, and that Ros-1 may be a receptor for Nell2 in RGCs.

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