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Shuster, S. A.

Publications and source records attributed to Shuster, S. A..

3 recordsLinked to original sources

The functional diversification of somatosensory neuron repertoires across Mammalia

The striking diversity of mammalian body forms and surfaces, lifestyles, and habitats prompts the question of how each species' somatosensory neuron repertoire accommodates such diversity. The visual and olfactory systems diversify by gaining and losing sensor/receptor genes and corresponding sensory cell types. Using multiomic single-cell analysis of dorsal root ganglia neurons from thirteen different mammalian species and cross-species functional studies enabled by cell-type-specific enhancer viruses, we show that mammals instead assemble species-specific, functionally distinct somatosensory neuron repertoires from a conserved set of neuron types (orthotypes). Repertoire diversification takes multiple forms: orthotype abundance scales with variable bodily traits like hair follicle density, facilitating relevant behaviors; sensor/receptor expression is shuffled across species, such that orthotypes can detect different stimuli in different species; and orthotypes split into functionally distinct, species-specific subtypes (paratypes). Thus, unlike other sensory systems, the mammalian somatosensory system diversifies through multifarious changes to conserved orthotypes, enabling adaptation to diverse habitats, lifestyles, and body forms.

neuroscience↗

Cell-surface proteomic profiling identifies CD72 as a regulator of microglial tiling

Microglial tiling--the phenomenon of consistent cell-to-cell distances and non-overlapping processes--is regarded as a qualitative indicator of homeostasis, but mechanisms of microglial tiling are unknown. We used cell-surface proximity labeling and mass spectrometry to profile the microglial cell-surface proteome in an in vitro model of homeostatic glial physiology and used single-cell RNA sequencing and public databases to identify candidate cell-surface proteins that might modulate tiling. We designed an image-based functional assay which measures six morphological/spatial readouts to screen these proteins for modulation of tiling. CD72, a coreceptor to the B cell receptor that is expressed by microglia, disrupted tiling; we validated its effects in vitro and in situ in organotypic hippocampal brain slices. Phosphoproteomic studies revealed that CD72 modulates pathways associated with cell adhesion, repulsive receptors, microglial activation, and cytoskeletal organization. These results lay the groundwork for further investigation of the functional roles of tiling in homeostasis and disease.

neuroscience↗

Transcription factor control of dendrite targeting via combinatorial cell-surface codes

Transcription factors specify the fate and connectivity of developing neurons. We investigate how a lineage-specific transcription factor, Acj6, controls the precise dendrite targeting of Drosophila olfactory projection neurons (PNs) by regulating the expression of cell-surface proteins. Quantitative cell-surface proteomic profiling of wild-type and acj6 mutant PNs in intact developing brains and a proteome-informed genetic screen identified PN surface proteins that execute Acj6-regulated wiring decisions. These include canonical cell adhesion molecules and proteins previously not associated with wiring, such as Piezo, whose mechanosensitive ion channel activity is dispensable for its function in PN dendrite targeting. Comprehensive genetic analyses revealed that Acj6 employs unique sets of cell-surface proteins in different PN types for dendrite targeting. Combinatorial expression of Acj6 wiring executors rescued acj6 mutant phenotypes with higher efficacy and breadth than expression of individual executors. Thus, Acj6 controls wiring specificity of different neuron types by specifying distinct combinatorial expression of cell- surface executors.

neuroscience↗