Project leader: Jesús Pujol-Martí
How neurons acquire a diverse repertoire of structural and functional properties in order to establish working neural circuits remains poorly understood. To address this question, we use the T4/T5 neurons of the Drosophila visual system as a model because of their genetic accessibility and the extensive knowledge we have about their morphology and physiology. The dendrites of T4 and T5 neurons represent the first processing stage in the fly visual system in which the direction of image motion is encoded. While T4 neurons respond to motion of brightness increments, T5 neurons detect motion of brightness decrements (Maisak et al., 2013). This specialization results from their dendrites arborizing in different neuropil regions (T4 dendrites in the medulla, T5 dendrites in the lobula) and therefore receiving synaptic input from different neuronal types. A common attribute of T4 and T5 neurons is the layer-specific innervation displayed by their dendrites and axons (Figure 1) (Fischbach and Dittrich, 1989), which is thought to support precise synaptic connectivity. We have found that SoxN and Sox102F, two members of the SOX family of transcription factors, are required in all T4 and T5 neurons during their maturation in order to restrict their dendrites and axons into single synaptic layers. When this process fails, some postsynaptic partners of T4/T5 neurons also exhibit aberrant morphologies, which affects the proper functioning of the fly motion sensing circuits (Figure 2) (Schilling et al., 2019).
Interestingly, both T4 and T5 neurons can be further subdivided into four subtypes, each responding exclusively to motion in one of the four cardinal directions (Maisak et al., 2013). Differences between T4/T5 neuron subtypes in directional tuning are thought to result from differences in the spatial organization of synapses they receive from an identical set of input neurons (Serbe et al., 2016; Arenz et al., 2017; Takemura et al., 2017; Shinomiya et al., 2019). How do these differences emerge during development? Since the orientation of each T4 and T5 dendritic arbor aligns with the neuron´s preferred direction of motion (Takemura et al., 2017; Shinomiya et al., 2019), our working hypothesis is that the direction in which a T4/T5 dendrite grows during development determines the arrangement of its synaptic inputs and, thus its direction selectivity. Our current work attempts to understand the cellular rules and underlying molecular mechanisms by which the four T4/T5 neuron subtypes acquire their distinctly oriented dendritic arbors. Understanding how T4/T5 neurons acquire their structural attributes during development will further help to link morphology, function and development in a single neuronal population, as well as to manipulate specific neuronal structural properties to reveal their role in neuronal computation.
Arenz A, Drews MS, Richter FG, Ammer G, Borst A (2017) The Temporal Tuning of the Drosophila Motion Detectors Is Determined by the Dynamics of Their Input Elements. Current biology : CB 27:929-944. DOI
Fischbach K-F, Dittrich APM (1989) The optic lobe of Drosophila melanogaster. I. A Golgi analysis of wild-type structure. Cell and Tissue Research 258:441-475.
Maisak MS, Haag J, Ammer G, Serbe E, Meier M, Leonhardt A, Schilling T, Bahl A, Rubin GM, Nern A, Dickson BJ, Reiff DF, Hopp E, Borst A (2013) A directional tuning map of Drosophila elementary motion detectors. Nature 500:212-216. DOI
Schilling T, Ali AH, Leonhardt A, Borst A, Pujol-Marti J (2019) Transcriptional control of morphological properties of direction-selective T4/T5 neurons in Drosophila. Development (Cambridge, England) 146. DOI
Serbe E, Meier M, Leonhardt A, Borst A (2016) Comprehensive Characterization of the Major Presynaptic Elements to the Drosophila OFF Motion Detector. Neuron 89:829-841. DOI
Shinomiya K et al. (2019) Comparisons between the ON- and OFF-edge motion pathways in the Drosophila brain. eLife 8. DOI
Takemura SY, Nern A, Chklovskii DB, Scheffer LK, Rubin GM, Meinertzhagen IA (2017) The comprehensive connectome of a neural substrate for 'ON' motion detection in Drosophila. eLife 6. DOI