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The Molecular Control of Zebrafish Isotocin Cell Development: A Potential Model for the Neurodevelopmental Causes of Autism and Prader-Willi Syndrome
Eaton, Jennifer Lynn

2006, PHD, Kent State University, School of Biomedical Sciences.
Altered oxytocin cell development and function are associated with several neuropsychiatric disorders, including autism and Prader-Willi Syndrome. However, the molecular control of oxytocin cell development is poorly understood. Zebrafish have been shown to be a powerful model for identifying and analyzing regulatory genes that control brain development. The objective of this dissertation was to establish the zebrafish as a model system to study the molecular genetic control of development of isotocin, homolog of oxytocin, producing cells. The central hypothesis of this proposal is that an evolutionarily conserved regulatory gene network consisting of Sim1, Otp, Arnt2 and Pou3f2, control the development of isotocin cells in the developing zebrafish hypothalamus. The following four specific aims were accomplished: Aim 1 characterized the zebrafish hypothalamo-neurohypophysial system (HNS) during development. This aim identified and characterized isotocin and vasotocin cells in the zebrafish hypothalamus. Aim 2 identified and characterized transcriptional regulatory genes controlling zebrafish isotocin cell development. Potential zebrafish orthologs of the mammalian oxytocin cell regulatory genes Sim1, Otp, Arnt2 and Pou3f2 were identified and screened for influencing isotocin cell development. Aim 3 confirmed the requirement of sim1 and otp in isotocin cell development and evaluated the genetic interactions between these genes. This study demonstrated sim1 and otp act in parallel pathways to control differentiation of isotocin cells. Aim 4 evaluated the role of two potential, equally related, homologs of mammalian Pou3f2 in zebrafish isotocin cell development, pou47 and brn1.2. Pou47 and brn1.2 were both found to be required for isotocin cell development and do not genetically interact to specify isotocin cellular identity. Aim 5 evaluated the genetic interaction of these Pou3f2 homologs with sim1 and otp in their control of zebrafish isotocin cell development. The data in this aim, along with a re-evaluation of the mouse literature, suggests these genes act combinatorially to specify isotocin cell development. Therefore, a new genetic model of this regulation is proposed. The rational for this proposal is that an elucidation of the molecular control of oxytocin (isotocin) cell development will contribute to an understanding of the neurodevelopmental causes of several neuropsychiatric diseases, such as autism and Prader-Willi Syndrome.
Eric Glasgow (Advisor)
266 p.

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Eaton, J. (2006). The Molecular Control of Zebrafish Isotocin Cell Development: A Potential Model for the Neurodevelopmental Causes of Autism and Prader-Willi Syndrome. (Electronic Thesis or Dissertation). Retrieved from https://etd.ohiolink.edu/

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Eaton, Jennifer. "The Molecular Control of Zebrafish Isotocin Cell Development: A Potential Model for the Neurodevelopmental Causes of Autism and Prader-Willi Syndrome." Electronic Thesis or Dissertation. Kent State University, 2006. OhioLINK Electronic Theses and Dissertations Center. 28 Apr 2015.

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Eaton, Jennifer "The Molecular Control of Zebrafish Isotocin Cell Development: A Potential Model for the Neurodevelopmental Causes of Autism and Prader-Willi Syndrome." Electronic Thesis or Dissertation. Kent State University, 2006. https://etd.ohiolink.edu/

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