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|Title:||Illuminating the Role of ERK Signaling in Early Zebrafish Embryonic Development Using Optogenetics|
|Abstract:||RASopathies are a family of developmental disorders caused by germline mutations in the Ras/MAPK pathway. The MAPK or ERK signaling cascade is a key signaling pathway in animal development, involved in cell proliferation, differentiation, and migration. Mutations in this pathway, such as those associated with RASopathies, cause phenotypes such as craniofacial dysmorphology, cardiac defects, and arteriovenous malformations. In model organisms like zebrafish, some of the developmental phenotypes caused by hyperactivation of ERK signaling mimic abnormalities seen in RASopathy patients, such as enlarged hearts in zebrafish compared to hypertrophic cardiomyopathy in human patients. This study focuses on the effects of diseased ERK signaling on the early developmental stages of the zebrafish embryo, when the first key cell fate decisions are being made. We provided ectopic ERK signals optogenetically and assayed the transcriptional responses of the embryo at multiple levels. Optogenetically activated embryos expressed upregulation of dorsal genes and downregulation of ventral genes. Furthermore, domains of cells expressing dorsal fate markers were expanded, while domains of ventral fate marker cells were reduced. In addition, we identified the presence of a new cell state found only in optogenetically activated embryos, that expresses genes involved in vascular system development. These findings indicate that ectopic ERK signaling causes a re-patterning of the dorsal-ventral axis, suggesting a re-patterning of the LPM, in addition to the early emergence of an arterial-venous specification event normally expected much later in development. This offers insight into enlarged hearts or arteriovenous malformations as RASopathy phenotypes.|
|Type of Material:||Princeton University Senior Theses|
|Appears in Collections:||Molecular Biology, 1954-2021|
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