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Faculty Advisors

Merlin Gnanapragasam

Description

Terminal differentiation in erythroid cells culminates in enucleation, a type of cytokinesis, where the nucleus is expelled from the cell. Improper cytokinesis and enucleation is due to a mutation in Erythroid Krüppel-like Factor (EKLF), an erythroid transcription factor, leading to Congenital Dyserythropoeitic Anemia IV (CDA’s) whose pathway remains to be understood. If EKLF is knocked out of mouse erythroid cells, the cells exhibit a failure in cytokinesis and enucleation with more megakaryocyte production. EKLF does have a role in allowing megakaryocyte erythroid cells to enter into erythropoiesis if the megakaryopoiesis genes are suppressed. Although, it is unknown if EKLF suppress megakaryocyte genes directly. I hypothesized that EKLF regulates genes involved in cytokinesis, enucleation, and multinucleation in megakaryocytes, and the failed regulation in erythroid EKLF null mouse cells and CDA IV patients leads to failures in cytokinesis and enucleation and a binucleate cell phenotype. A literature search was conducted to learn about genes involved in cytokinesis and enucleation in erythroid cells and whether those genes play a role in CDA’s and multinucleation in megakaryocytes. Comparison of the data from the RNA sequence of EKLF +/+ and EKLF -/- mouse cells with genes that are pertinent for megakaryopoiesis may lead to the discovery of a subset of megakaryocyte genes that are abnormally expressed in EKLF-/- cells. Overall, our study shows that when the regulation of genes that contains the multinucleated phenotype in megakaryocytes are mis regulated the end result can lead to a failure in cytokinesis, a binucleate phenotype and enucleation defects.

Publication Date

2020

Department

Biological Sciences

Student Publication

This item is part of the McNair Scholars Program.

EKLF Mediated Regulation of Cytokinesis, Erythroid Enucleation, and Megakaryopoiesis During Terminal Differentiation and Congenital Dyserythropoietic Anemia

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