Haji Ali, Aicha (2025): Polarized dendritic development of motion-sensing neurons in Drosophila. Dissertation, LMU München: Graduate School of Systemic Neurosciences (GSN) |
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Abstract
In all sighted animals the ability to see motion is crucial for survival, driving extensive research into the neuronal circuits responsible for motion vision across various model organisms. Motion vision in Drosophila has been a cornerstone in systems neuroscience, with recent interest focusing on how this circuitry develops and how the dendritic growth of individual neurons contributes to the overall circuit architecture. T4 and T5 (T4/T5) neurons, serving as the primary motion detectors in the Drosophila motion detection circuit, play a vital role in the fly’s ability to perceive motion. These neurons exhibit highly asymmetric dendrites, organized into three functional compartments: proximal, medial, and distal. This compartmentalization stems from the spatially segregated connections formed by T4/T5 neurons with their respective input partners, despite these inputs being repeated in every column that T4/T5 neurons extend into. T4/T5 neurons are divided into four distinct subtypes: a, b, c, and d, each attuned to detecting motion in one of the four cardinal directions. A key morphological distinction among T4/T5 neurons across subtypes is their subtype-specific dendritic orientation, where dendritic branches predominantly extend in the direction opposite to the subtype’s preferred motion direction. This subtype-specific dendritic orientation, alongside their functional compartmentalization, underlies the direction-selective responses of T4/T5 neurons, making them an excellent model for investigating type-specific dendritic growth and its implications in circuit formation. Throughout my PhD, my focus centered on the post-mitotic development of T4/T5 neurons, particularly their dendritic growth. The results of my research are included chronologically in this cumulativestyle dissertation in three manuscripts, two of which are already published in peer-reviewed journals. In manuscript 1, we conducted a gene screening study using an existing RNA sequencing dataset for mature T4/T5 neurons, coupled with an RNA interference (RNAi) approach. We identified two transcription factors — SoxNeuro and Sox102F — that regulate shared morphological features in T4/T5 dendrites across subtypes. Manipulating the expression levels of either SoxN or Sox102F in T4/T5 neurons led to the mistargeting of their dendrites and axons in their respective neuropils. These morphological changes significantly impaired the flies’ motion detection ability. In manuscript 2, our objective was to uncover the transient transcriptional programs guiding the post-mitotic development of subtype-specific morphological features in T4/T5 neurons. Employing single-cell RNA sequencing at various developmental stages, we identified transcriptional codes distinguishing between subtypes throughout development. Furthermore, we showed how the expression profile of two transcriptional factors, Bifid and Grain, provide a binary combinatorial code to determine the subtype-identity in T4/T5 neurons. In Manuscript 3, we focused on T4 neurons as we sought to discern whether all T4 neurons adhere to a uniform dendritic growth program or if distinct T4 subtypes exhibit varied growth patterns during dendritic development. Using time-lapse imaging, we observed discrepancies in growth dynamics among the subtypes, presumably influenced by the hexagonal arrangement of columns within the optic lobe. However, from a neuron egocentric perspective, we were able to show that all T4 neurons fundamentally adhere to the same dendritic growth program. Our imaging revealed that all T4 neurons initially extend their dendrites within their putative proximal compartment before advancing into the medial compartment. We envisage that this sequential compartmentalized growth pattern is essential for establishing the functional compartmentalization within T4 dendrites. In summary, our research sheds light on the transcriptional program governing the post-mitotic development of T4/T5 neurons, revealing the combinatorial code crucial for determining their subtype identity. Additionally, we unraveled the growth program guiding T4 dendrites in establishing their asymmetric, compartmentalized architecture.
Dokumententyp: | Dissertationen (Dissertation, LMU München) |
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Themengebiete: | 500 Naturwissenschaften und Mathematik
500 Naturwissenschaften und Mathematik > 570 Biowissenschaften, Biologie |
Fakultäten: | Graduate School of Systemic Neurosciences (GSN) |
Sprache der Hochschulschrift: | Englisch |
Datum der mündlichen Prüfung: | 7. März 2025 |
1. Berichterstatter:in: | Borst, Alexander |
MD5 Prüfsumme der PDF-Datei: | f8dcf56566d81419f8afd3b68aed0808 |
Signatur der gedruckten Ausgabe: | 0001/UMC 31126 |
ID Code: | 35107 |
Eingestellt am: | 03. Apr. 2025 14:15 |
Letzte Änderungen: | 03. Apr. 2025 14:18 |