Transcriptional profiling of multi-transmitter neurons in the zebrafish forebrain
Datum
2021-09-13
Autor:innen
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Verlag
University of Oregon
Zusammenfassung
Neurotransmitter phenotype is the hallmark of neuronal identity. Neurons are classified based on the neurotransmitters they release. At the inception of the discipline of neuroscience was a fascination with the structure of neurons and morphology of brain tissue. The pioneering work of Santiago Ramon y Cajal (1852-1934) and Henreich Wilhelm Waldeyer(1836-1921) ushered in the famous Neuron Doctrine, which posited that neurons are not only structural units of the nervous system but as trophic, functional, and genetic units. Deciphering the neurotransmitter identity of neurons has been a principal reference point for making interpretations of their function during specific behaviors. In addition, there is a wealth of evidence which shows that neurons can synthesize and release multiple neurotransmitters. However, the development of such neurons and the factors that drive their development has been largely unexplored. Researchers have often narrowed their investigations to establishing the presence of a single neurotransmitter. Mapping these neurons across the vertebrate phyla has not received nearly enough attention though this is conceivably important in understanding common phylogenetic traits. In addition, it is unknown if multi-transmitter neurons attain this identity in a sequential manner or they develop different neurotransmitters at the same time.
To address these questions, I utilized the zebrafish (Danio rerio) as a model system, I characterized a transgenically defined population of multi-transmitter neurons in the zebrafish forebrain. These neurons which are important in social orienting behavior, synthesize both Acetylcholine and GABA and this study was the first to establish this. My work demonstrates that for this cluster of neurons, the neurotransmitters are co-expressed from the first day of development, and this co-expression persists till adulthood. Further, I identified a constellation of specific marker genes expressed by these neurons, which together with three LIM Homeobox Transcription factor genes enables us to map similar neurons in other vertebrates with great accuracy. I also tested a novel hypothesis on specification of these multi-transmitter neurons by LIM homeobox transcription factor genes. In conclusion, the comprehensive characterization contained this work presents a great platform to tease apart fundamental questions on the impact of different perturbations on the development of neurons.
Beschreibung
Schlagwörter
Cholinergic, Evolutionarily conserved, GABA, LIM homeobox transcription factor gene, Multi-transmitter neurons, Telencephalon