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Grant: Discovery Grants Program - Individual

University of Manitoba

$60,000.00

Radial-glial stem cell development and plasticity in the adult zebrafish brain

FY 2024-25

Summary
The long-term objective of my research program is to understand adult neural stem cell activity in the central nervous system of vertebrates. Most animals retain lifelong populations of adult neural stem cells in subregions of the brain, commonly known as the `neurogenic niche'. These cells produce newborn neurons throughout the life of animals, and in mammals and birds appear to play an important role in animal behaviour, learning and memory. In recent years, it has been discovered that different populations of adult neural stem cells react differently to various forms of stimuli or injury. This has proposed that adult neural stem cell populations located in different neurogenic niches may contribute to distinct functions in order to keep the central nervous system in balance. Very little however is understood towards how different populations of adult neural stem cells behave over development or under different biological contexts. This is particularly true in leading fish models, such as the zebrafish and medaka, which maintain some of the largest populations of adult neural stem cells and diversity of neurogenic niches. The proposed research will use the zebrafish model to study the activity of radial-glial brain stem cells across separate neurogenic niches and under different biological conditions. The zebrafish provides a valuable experimental system to examine these questions, owing to its adult neurogenic niches in brain structures that process both cognitive and sensory information, and remarkable neuro-regenerative potential. How populations of radial-glia change as neurogenic niches take on an adult form remains unclear. I will identify the dynamic changes in radial-glial populations from larval to adult stages and how these changes may be controlled at the molecular level. While other vertebrates, such as rodents, show a direct link between adult neural stem cells and learning species-specific behaviours, it is unknown whether this holds true in fish models. I will address this question by examining whether radial-glial populations are required to perform learning tasks in adult zebrafish. Finally, to better understand the activity of similar radial-glial stem cell types in different neurogenic niches and under different contexts, I will define radial-glial behaviour and gene regulation following enrichment and injury. Collectively, the proposed research will advance our fundamental knowledge of adult neural stem cell activity in teleost models while training at least 9 HQP. My work will serve to broaden our understanding of adult neural stem cell activity beyond the small number of vertebrates studied to date, and identify mechanisms in the zebrafish that may be present in cell populations of the central nervous system across major vertebrate and invertebrate groups. This will be important for moving towards a comparative and evolutionary understanding of the lifelong role and regulation of neural stem cells.
Program
Discovery Grants Program - Individual
Location
Manitoba, Canada
Recipient Type
Academia
Type
Grant
Source
NSERC's Awards Data

As published

Application id
RGPIN-2019-05357
Name nom
Lindsey, Benjamin
Department département
Human Anatomy and Cell Science
Organization id
19
Institution établissement
University of Manitoba
Province en
Manitoba
Province fr
Manitoba
Country en
CANADA
Country fr
CANADA
Fiscal year exercice financier
2024
Competition year année de concours
2019
Award amount
60000
Program id
RGPIN
Program name en
Discovery Grants Program - Individual
Program name fr
Programme de subventions à la découverte - individuelles
Group en
DISCOVERY RESEARCH
Group fr
RECHERCHE AXÉE SUR LA DÉCOUVERTE
Committee code
1501
Committee name en
Genes, Cells and Molecules
Committee name fr
Gènes, cellules et molécules
Area of application code
1201
Area of application group en
Advancement of knowledge
Area of application group fr
Avancement des connaissances
Area of application en
Life sciences (including biotechnology)
Area of application fr
Sciences de la vie (y compris biotechnologie)
Research subject code
5104
Research subject group en
Cell biology
Research subject group fr
Biologie cellulaire
Research subject en
Cell division
Research subject fr
Division cellulaire
Field of research list names en
Not available
Field of research list names fr
Non disponible
Socioeconomic objective list names en
Not available
Socioeconomic objective list names fr
Non disponible
Application title
Radial-glial stem cell development and plasticity in the adult zebrafish brain
Keywords
zebrafish transgenic lines; adult neural stem cell plasticity; neurogenic niche development; quiescent and active radial-glia; stem cell heterogeniety; cell proliferation and differentiation; notch signalling; confocal and electron microscopy; cellular and molecular regulation; adult neurogenesis and learning
Application summary
The long-term objective of my research program is to understand adult neural stem cell activity in the central nervous system of vertebrates. Most animals retain lifelong populations of adult neural stem cells in subregions of the brain, commonly known as the `neurogenic niche'. These cells produce newborn neurons throughout the life of animals, and in mammals and birds appear to play an important role in animal behaviour, learning and memory. In recent years, it has been discovered that different populations of adult neural stem cells react differently to various forms of stimuli or injury. This has proposed that adult neural stem cell populations located in different neurogenic niches may contribute to distinct functions in order to keep the central nervous system in balance. Very little however is understood towards how different populations of adult neural stem cells behave over development or under different biological contexts. This is particularly true in leading fish models, such as the zebrafish and medaka, which maintain some of the largest populations of adult neural stem cells and diversity of neurogenic niches. The proposed research will use the zebrafish model to study the activity of radial-glial brain stem cells across separate neurogenic niches and under different biological conditions. The zebrafish provides a valuable experimental system to examine these questions, owing to its adult neurogenic niches in brain structures that process both cognitive and sensory information, and remarkable neuro-regenerative potential. How populations of radial-glia change as neurogenic niches take on an adult form remains unclear. I will identify the dynamic changes in radial-glial populations from larval to adult stages and how these changes may be controlled at the molecular level. While other vertebrates, such as rodents, show a direct link between adult neural stem cells and learning species-specific behaviours, it is unknown whether this holds true in fish models. I will address this question by examining whether radial-glial populations are required to perform learning tasks in adult zebrafish. Finally, to better understand the activity of similar radial-glial stem cell types in different neurogenic niches and under different contexts, I will define radial-glial behaviour and gene regulation following enrichment and injury. Collectively, the proposed research will advance our fundamental knowledge of adult neural stem cell activity in teleost models while training at least 9 HQP. My work will serve to broaden our understanding of adult neural stem cell activity beyond the small number of vertebrates studied to date, and identify mechanisms in the zebrafish that may be present in cell populations of the central nervous system across major vertebrate and invertebrate groups. This will be important for moving towards a comparative and evolutionary understanding of the lifelong role and regulation of neural stem cells.