Defining the Role of Proneural Genes in Neurogenesis, Specification, and Migration of Mouse VMH Neurons

Aslan Pour Kal Bolandi, Shaghayegh

Defining the Role of Proneural Genes in Neurogenesis, Specification, and Migration of Mouse VMH Neurons

dc.contributor.advisor	Kurrasch-Orbaugh, Deborah M.
dc.contributor.author	Aslan Pour Kal Bolandi, Shaghayegh
dc.contributor.committeemember	Childs, Sarah J.
dc.contributor.committeemember	Yang, Guang
dc.date	2020-02
dc.date.accessioned	2020-01-03T20:35:45Z
dc.date.available	2020-01-03T20:35:45Z
dc.date.issued	2020-01
dc.description.abstract	The ventromedial hypothalamus (VMH) is a hypothalamic nucleus important for controlling satiety and reproductive behaviors, among other physiologies. Despite these important roles, the genetic programs driving VMH development are just starting to be explored. Since proneural genes are one of the key drivers of neurodevelopment throughout the brain, we asked whether the proneural genes Achaete-scute homolog 1 (Ascl1) and Neurogenin 2 (Neurog2) play key roles in VMH development, given their expression in VMH progenitors. My hypothesis is that proneural genes play a role in neurogenesis, cell fate decisions and/or in the migration of VMH neurons. To start, I investigated the role of Ascl1 in the specification and fate of VMH neurons. I showed that Ascl1+ lineages give rise to a large population of VMH neurons and that Ascl1 is necessary for promoting VMHDM and VMHC neuronal specification. In addition, my results revealed that Ascl1 played an important role in the timing of neurogenesis within the tuberal hypothalamus. Next, I examined the role of Neurog2 in the neurogenesis of VMH specific neurons and showed that Neurog2 was necessary for timely cell cycle exit and birth of VMH neurons. Moreover, I showed Neurog2 was required for proper development of the VMH at both early and late embryonic developmental stages. Neurog2 is particularly important for proper differentiation of VMHVL neurons. Finally, I studied the role of Ascl1 and Neurog2 in cell sorting within the maturing VMH. My results revealed that between E15.5 to E17.5 and in the absence of either Ascl1 or Neurog2, there is a change in the final positioning of cells. Since Ascl1 and Neurog2 can act through Rnd3 and Rnd2 proteins to regulate cortical neuronal migration, I asked whether Ascl1 and Neurog2 potentially employ a similar mechanism to regulate VMH cell sorting. My results showed both Rnd2 and Rnd3 were expressed within the VMH nucleus across VMH embryonic developmental stages. In addition, at later stages such as E15.5 and E19.5, the expression of both Rnd2 and Rnd3 was significantly decreased in the absence of Neurog2 and Ascl1 respectively. Finally, using a live cell imaging technique, I assayed neuronal movement during cell sorting events within the VMH. Together, these studies provide insight into the varying roles proneural genes play in the developing tuberal hypothalamus.	en_US
dc.identifier.citation	Aslan Pour Kal Bolandi, S. (2020). Defining the role of proneural genes in neurogenesis, specification, and migration of mouse VMH neurons (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.	en_US
dc.identifier.doi	http://dx.doi.org/10.11575/PRISM/37401
dc.identifier.uri	http://hdl.handle.net/1880/111424
dc.language.iso	eng	en_US
dc.publisher.faculty	Cumming School of Medicine	en_US
dc.publisher.institution	University of Calgary	en
dc.rights	University of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.	en_US
dc.subject	VMH	en_US
dc.subject	proneural genes	en_US
dc.subject	development	en_US
dc.subject	cell fate decision	en_US
dc.subject	neurogenesis	en_US
dc.subject	cell sorting	en_US
dc.subject.classification	Neuroscience	en_US
dc.title	Defining the Role of Proneural Genes in Neurogenesis, Specification, and Migration of Mouse VMH Neurons	en_US
dc.type	doctoral thesis	en_US
thesis.degree.discipline	Medicine – Neuroscience	en_US
thesis.degree.grantor	University of Calgary	en_US
thesis.degree.name	Doctor of Philosophy (PhD)	en_US
ucalgary.item.requestcopy	true	en_US