Maraki Negesse

Participant: PROMISE AGEP Research Symposium

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Maraki Negesse

Department: Biological Sciences

Institution: University of Maryland, Baltimore County (UMBC)

2018 ABSTRACT

From a birth brain defect to underlying genetics

Neural tube defects (NTDs) occur when brain morphogenesis, commonly referred to as neurulation, is impaired during early stages of development. Neurulation is the process by which the neural tube, the early precursor of the brain and the spinal cord, forms. The most common NTD is Holoprosencephaly (HPE), affecting 1 in 250 conceptuses. HPE is a morphological defect of the forebrain, manifested in most several cases by fusion of the left and right brain hemispheres. Despite the importance of the forebrain for regulation of essential visceral, reproductive and physiological functions, little is understood about how this brain region develops and how NTDs such as HPE arise. We are interested in studying the early stages of neurulation, leading to a fully formed neural tube in the prospective forebrain. We aim to provide a cellular and molecular analysis of the mechanistic events during neurulation and how they are regulated. We further aim to provide a groundwork to investigate impaired processes that impact neurulation and result in HPE symptoms.

 

2017 ABSTRACT

Anoxia mediated regulation of microtubule dynamics

Entering a hypometabolic stage is a survival means adopted by many organisms when faced with harsh conditions, such as low oxygen levels. However, despite the importance of this physiological adaptation little is understood about the pathways that trigger it. The goal of my research project has been to characterize this process in the zebrafish. Zebrafish embryos can survive up to 50 hours in anoxia (zero oxygen) by arresting development, a mechanism that conserves ATP and contributes to hypometabolism. During zebrafish epiboly, developmental arrest is achieved by pausing the spread of the blastoderm over the yolk. Epiboly is thought to be driven by the remodeling of the yolk microtubule network, which provides a pulling force on the blastoderm. Indeed, drugs that either stabilize or de-stabilize microtubules can cause a delay or blockage of epiboly, raising the possibility that signaling pathways that promote anoxia-induced arrest during epiboly may impinge upon the microtubule cytoskeleton. Based on these observations, we hypothesized that changes in microtubule stability under anoxia may be a key mechanism driving developmental arrest. To test this hypothesis, I used a transgenic line expressing double cortin-like kinase 2 (dclk2) fused with GFP, which allows indirect visualization of microtubules. 50% epiboly stage zebrafish embryos were subjected to an hour of anoxia or normoxia. Imaging was performed using confocal microscopy. Preliminary data suggest that the anoxia-subjected embryos show some disruption in the network of yolk microtubules compared to normoxic controls. Identifying the different molecules involved might better our understanding of anoxia-mediated arrest.

 

BIOGRAPHICAL SKETCH

I am a second year PhD student in the Biological Sciences at the University of Maryland Baltimore County, in the Brewster laboratory. My research interest focuses on developmental, cellular and molecular biology. I am currently studying the cellular events underlying forebrain morphogenesis. I am an LSAMP Bridges to the Doctorate and an IMSD Meyerhoff fellow. Prior to graduate school, I earned a Bachelor of Science in Chemistry in 2011 and a Bachelor of science in Biochemistry and Molecular Biology in 2016.

 

GENERAL SUMMARY OF GRADUATE RESEARCH

Neurulation is the process by which the neural tube, the precursor of the brain and the spinal cord, forms during early development. The neural plate, a layer of epithelialized neuroectodermal cells, undergoes dramatic morphogenetic changes to shape the neural tube. In the prospective forebrain, neurulation occurs in a unique way, as it is tightly linked to morphogenesis of the eye field. Fate maps of vertebrate embryos reveal that the prospective forebrain occupies the lateral edge of the eye field. The optic vesicles evaginate as neurulation proceeds and the neural tube is positioned in between the eyes. Despite the forebrain being the largest part of the brain and regulating essential physiological and cognitive functions, very little is known about the cellular processes that shape the neural tube in the prospective forebrain. Defects in the mechanism of forebrain morphogenesis lead to neural tube defects (NTDs) such as holoprosencephaly (HPE). HPE occurs in 1 in 250 conceptuses and is the most frequent forebrain NTD. My thesis proposal aims to investigate the cellular behaviors that drive forebrain morphogenesis in the zebrafish embryo and identify key underlying signaling molecules implicated in HPE.

 

SELECTED LIST OF PRESENTATIONS AND PUBLICATIONS

  1. A strategy for using zebrafish to assess variants associated with neural tube defects. Poster presentation, International Conference on Neural Tube Defects, October 2017
  2. Anoxia-mediated regulation of microtubule dynamics. Poster presentation, Graduate Research Conference, UMBC, March 2017; Spring 2017 PROMISE Research Symposium & Professional Development Conference, February 2017

 

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