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Cortical neuron maturation is independently inhibited by p53 and promoted by Kinesin-6 function

Presenters Name: 
Madison Hecht
Co Presenters Name: 
Primary Research Mentor: 
Noelle Dwyer
Secondary Research Mentor: 
9:30 - 10:15
Time of Presentation: 
2019 - 9:30am to 10:15am
Newcomb Hall Ballroom
Presentation Type: 
Presentations Academic Category: 
Grant Program Recipient: 
Harrison Undergraduate Research Grant

p53 is a known regulator of multiple facets of cell behavior, including the maturation of several cell types. However, very little is known about the role of p53 in cortical neuron growth and maturation. Here, we use a p53 knockout mouse to investigate the role of p53 in the normal development of cortical neurons. We find that p53 deletion accelerates cortical neuron polarization in vitro, compelling neurons to more rapidly transition out of a multipolar state, extend their axons and become polarized. We additionally show that p53 mutant neurons have more mature morphological characteristics, including longer and thinner axons, thinner minor neurites, shorter filopodia, and higher proportions of acetylated tubulin. Bulk RNA sequencing data confirms these findings as genes involved in axonogenesis are upregulated in p53 mutant cortices. We previously discovered that p53 deletion rescues microcephaly in a kinesin-6 (Kif20b) mutant, illustrating p53’s important role in responding to defects in cortical development. Thus, here we also evaluate how p53 deletion affects the atypical neuron polarization and morphology found within the Kif20b mutant cortex. Interestingly, we find that the co-deletion of p53 and Kif20b does not rescue these maturation defects and that p53 and Kif20b function independently with opposing effects.