Regulation of gene expression by growth differentiation factor 15 in the developing mouse and human neocortex

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dc.contributor.authorMohamad, Ruby
dc.contributor.examiningcommitteeDocker, Margaret (Biological Sciences)
dc.contributor.examiningcommitteeLee, Jae-Hyeok (Biological Sciences)
dc.contributor.supervisorXing, Lei
dc.date.accessioned2025-05-23T18:50:02Z
dc.date.available2025-05-23T18:50:02Z
dc.date.issued2025-04
dc.date.submitted2025-05-23T18:50:02Zen_US
dc.degree.disciplineBiological Sciences
dc.degree.levelBachelor of Science (B.Sc.)
dc.description.abstractThe evolution of the neocortex, specifically its expansion, is the key advancement that made higher cognitive abilities possible. Humans today have a neocortex that constitutes up to two-thirds of their overall brain mass. This expansion reflects increased and prolonged activity of neural progenitor cells (NPCs), which give birth to neurons during fetal cortical development. Growth differentiation factor 15 (GDF15) is a cell-extrinsic signal that has previously been found to promote basal progenitor proliferation, one of the main classes of NPCs critical to human brain development and evolution. Previously, the Xing Lab discovered several potential downstream targets that could be regulated by GDF15 in the fetal human neocortex, including Dachshund Family Transcription Factor 1 (DACH1), Glypican 6 (GPC6), Semaphorin 5A (SEMA5A), and Shroom Family Member 3 (SHROOM3). All of which have been reported to have various roles in neurodevelopment. In this study, we manipulated GDF15 levels in the developing mouse and human neocortex to understand its regulatory effect on the potential downstream targets. My range-finding experiment indicated a concentration-dependent increase in mRNA levels of the downstream targets, with the most increase observed in fetal human neocortical tissue incubated with 100ng/ml recombinant human GDF15 protein. Knockout of the GDF15 gene in embryonic mice revealed decreased mRNA levels of all the downstream targets. Furthermore, adult GDF15 knockout transgenic mice exhibited a decrease in interneuron and deep-layer neuron numbers. My findings are consistent with the notion that GDF15 regulates NPC proliferation through these downstream targets, contributing to long-term effects on neuron abundance in the adult brain.
dc.identifier.urihttp://hdl.handle.net/1993/39089
dc.language.isoeng
dc.subjectgrowth differentiation factor 15
dc.subjectGDF15
dc.subjectneurodevelopment
dc.subjectmice
dc.subjecthumans
dc.subjectgene expression
dc.titleRegulation of gene expression by growth differentiation factor 15 in the developing mouse and human neocortex
local.author.affiliationFaculty of Science::Department of Biological Sciences
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