Investigating genetic and environmental factors controlling functional development of the brain
It is widely known that the developing brain is shaped by a combination of both genetic and environmental factors, however the mechanisms that dictate the consequences of the interactions of these two factors at the cellular and molecular levels are still largely unknown. The Bergeron Lab has a long-term goal to investigate how specific molecular genetic pathways and distinct environmental contexts contribute to altered brain formation and function. We study these conserved genetic pathways, temporal and spatial gene expression, neuroanatomy, and behaviors in an in vivo genetic model system, the zebrafish (Danio rerio) - a rapidly developing and relatively transparent vertebrate that humans share ~70% of their genetic information with. Fertilization of zebrafish eggs occurs externally allowing us to manipulate the environments within which they are raised very easily and early on, starting at just the one-cell stage of embryonic development. In addition a single female zebrafish can produce ~300 eggs per spawning, allowing us to monitor large groups of genetically related individuals undergoing synchronous stages of development in our weekly studies.
Our current focus is on some of the earliest expressed transcription factor encoding genes in the nervous system. These transcription factors are highly conserved in their expression patterns and also presumably in their genetic targets across multiple organisms, though we will explore this further. In the zebrafish we can study specific classes of neurons based on their gene expression profiles and functions from the moment that they are born in the embryo through adulthood in both living and fixed preparations using microscopy and a variety of existing and readily generated molecular genetic tools to make transgenic zebrafish lines. With now improved targeted mutagenesis strategies we can also alter any gene of interest and observe the resulting neuroanatomical and behavioral changes throughout the mutant verses wild type zebrafish lifetime.
Our genetic, environmental, and observed neuroanatomical changes can also be linked to alterations in many sensory driven behaviors in the fish starting when they are just five days old. Using this model systems approach we hope to better understand some of the cellular and molecular mechanisms that underlie human neurodevelopmental disorders that are accompanied by changes in sensory driven behaviors.
Development of neural circuits for sensory processing
Disrupted sensory processing has been reported as a comorbidity in individuals with neurodevelopmental disorders such as ASD. One aim of our lab is to elucidate the molecular genetic pathways that direct the development and ultimately the function of specific neuronal circuits mediating sensory processing; primarily visual. To do this we are using a combination of microscopy, molecular genetic tools, and behavioral and neuroanatomical analyses.
Current projects are focused on the characterization of a zebrafish mutant exhibiting defective locomotion and sensory processing in the presence of different environmental stimuli. Ongoing work will elucidate the molecular mechanisms directing the development of the underlying neural circuitry across distinct brain regions and reveal how these brain regions integrate sensory information from the environment. We hypothesize this work will help identify important genes and circuits and direct the generation of novel interventions for human neurodevelopmental disorders.
Neural control of growth, reproduction, and homeostasis
A second aim of the lab is to study the development of neural pathways directing critical processes for organism survival including growth, reproduction, and homeostasis. We have already established a zebrafish mutant lacking a critical transcription factor for normal growth and development. Similar to the mouse transcription factor mutant, our zebrafish mutants are smaller than their wild type siblings due to a reduction of growth hormone (gh1), a key HPA/I axis hormone that serves as a chemical messenger between the brain and the endocrine system. However, unlike the mouse mutant, our zebrafish mutant survives until adulthood. This advantage allows the investigation of the neuronal circuitry beginning in the hypothalamus that directs the observed phenotypes throughout the lifetime of the animal. The hypothalamus is an essential brain region for everyday homeostatic regulation in fish and mammals, thus we will elucidate the development and function of novel circuitry in zebrafish that may play analogous roles in humans.
It is widely known that the developing brain is shaped by a combination of both genetic and environmental factors, however the mechanisms that dictate the consequences of the interactions of these two factors at the cellular and molecular levels are still largely unknown. The Bergeron Lab has a long-term goal to investigate how specific molecular genetic pathways and distinct environmental contexts contribute to altered brain formation and function. We study these conserved genetic pathways, temporal and spatial gene expression, neuroanatomy, and behaviors in an in vivo genetic model system, the zebrafish (Danio rerio) - a rapidly developing and relatively transparent vertebrate that humans share ~70% of their genetic information with. Fertilization of zebrafish eggs occurs externally allowing us to manipulate the environments within which they are raised very easily and early on, starting at just the one-cell stage of embryonic development. In addition a single female zebrafish can produce ~300 eggs per spawning, allowing us to monitor large groups of genetically related individuals undergoing synchronous stages of development in our weekly studies.
Our current focus is on some of the earliest expressed transcription factor encoding genes in the nervous system. These transcription factors are highly conserved in their expression patterns and also presumably in their genetic targets across multiple organisms, though we will explore this further. In the zebrafish we can study specific classes of neurons based on their gene expression profiles and functions from the moment that they are born in the embryo through adulthood in both living and fixed preparations using microscopy and a variety of existing and readily generated molecular genetic tools to make transgenic zebrafish lines. With now improved targeted mutagenesis strategies we can also alter any gene of interest and observe the resulting neuroanatomical and behavioral changes throughout the mutant verses wild type zebrafish lifetime.
Our genetic, environmental, and observed neuroanatomical changes can also be linked to alterations in many sensory driven behaviors in the fish starting when they are just five days old. Using this model systems approach we hope to better understand some of the cellular and molecular mechanisms that underlie human neurodevelopmental disorders that are accompanied by changes in sensory driven behaviors.
Development of neural circuits for sensory processing
Disrupted sensory processing has been reported as a comorbidity in individuals with neurodevelopmental disorders such as ASD. One aim of our lab is to elucidate the molecular genetic pathways that direct the development and ultimately the function of specific neuronal circuits mediating sensory processing; primarily visual. To do this we are using a combination of microscopy, molecular genetic tools, and behavioral and neuroanatomical analyses.
Current projects are focused on the characterization of a zebrafish mutant exhibiting defective locomotion and sensory processing in the presence of different environmental stimuli. Ongoing work will elucidate the molecular mechanisms directing the development of the underlying neural circuitry across distinct brain regions and reveal how these brain regions integrate sensory information from the environment. We hypothesize this work will help identify important genes and circuits and direct the generation of novel interventions for human neurodevelopmental disorders.
Neural control of growth, reproduction, and homeostasis
A second aim of the lab is to study the development of neural pathways directing critical processes for organism survival including growth, reproduction, and homeostasis. We have already established a zebrafish mutant lacking a critical transcription factor for normal growth and development. Similar to the mouse transcription factor mutant, our zebrafish mutants are smaller than their wild type siblings due to a reduction of growth hormone (gh1), a key HPA/I axis hormone that serves as a chemical messenger between the brain and the endocrine system. However, unlike the mouse mutant, our zebrafish mutant survives until adulthood. This advantage allows the investigation of the neuronal circuitry beginning in the hypothalamus that directs the observed phenotypes throughout the lifetime of the animal. The hypothalamus is an essential brain region for everyday homeostatic regulation in fish and mammals, thus we will elucidate the development and function of novel circuitry in zebrafish that may play analogous roles in humans.