Biology subjects

Xiao, Q.

Publications and source records attributed to Xiao, Q..

4 recordsLinked to original sources

bioRxiv2018

Stereotyped Terminal Axon Branching of Leg Motor Neurons Mediated by IgSF Proteins DIP-α and Dpr10

The ability of animals to perform coordinated movements depends on the precise organization of neural circuits controlling motor function. Motor neurons (MNs), which are key components of these circuits, must project their axons out of the central nervous system and form precise terminal branching patterns at specific muscles in the periphery. By focusing on the Drosophila adult leg neuromuscular system we show that the stereotyped terminal branching of a subset of leg MNs is mediated by interacting transmembrane Ig superfamily (IgSF) proteins DIP- and Dpr10, present in MNs and target muscles, respectively. Importantly, the DIP-/Dpr10 interaction is needed only after MN axons reach the vicinity of their muscle targets. Live imaging of this process suggests that precise terminal branching patterns are gradually established by DIP-/Dpr10-dependent interactions between fine axon filopodia and developing muscles. Further, different leg MNs depend on the DIP- and Dpr10 interaction to varying degrees that correlate with the morphological complexity of the MNs and their muscle targets, suggesting that some MNs depend upon multiple sets of interacting proteins to establish terminal axon branching.

neuroscience↗

bioRxiv2018

Transsynaptic interactions between IgSF proteins DIP-α and Dpr10 are required for motor neuron targeting specificity in Drosophila

The Drosophila larval neuromuscular system provides an ideal context in which to study synaptic partner choice, because it contains a small number of pre- and postsynaptic cells connected in an invariant pattern. The discovery of interactions between two subfamilies of IgSF cell surface proteins, the Dprs and the DIPs, provided new candidates for cellular labels controlling synaptic specificity. Here we show that DIP- is expressed by two identified motor neurons, while its binding partner Dpr10 is expressed by postsynaptic muscle targets. Removal of either DIP- or Dpr10 results in loss of specific axonal branches and NMJs formed by one motor neuron, MNISN-1s, while other branches of the MNISN-1s axon develop normally. The temporal and spatial expression pattern of dpr10 correlates with muscle innervation by MNISN-1s during embryonic development. We propose a model whereby DIP- and Dpr10 on opposing synaptic partners interact with each other to generate proper motor neuron connectivity.

neuroscience↗

bioRxiv2018

Multiple modulation synthesis with high spatial resolution for noninvasive deep neurostimulation

Noninvasive neurostimulation plays a pivotal role in direct control of neural circuit and modulating neuronal function. However, it is difficult to balance both spatial focality and depth of penetration in stimulating deep neurons. Here, we designed time-division, frequency & polarity modulation synthesis (TMFPMS) for stimulating deep neurons noninvasively with low-frequency envelope. We demonstrated its spatial resolution: mm-level via computational simulation including finite element analysis and Hodgkin-Huxley action potential model. Taken together, the results of this study indicate that TMFPMS neurostimulation with high spatial resolution is steerable and may replace traditional implanted electrode.

neuroscience↗

bioRxiv2018

Genetic variants associated with Alzheimer's disease confer different cerebral cortex cell-type population structure

Alzheimers disease (AD) is characterized by neuronal loss and astrocytosis in the cerebral cortex. However, the effects of brain cellular composition are often ignored in high-throughput molecular studies. We developed and optimized a cell-type specific expression reference panel and employed digital deconvolution methods to determine brain cellular distribution in three independent transcriptomic studies. We found that neuronal and astrocyte proportions differ between healthy and diseased brains and also among AD cases that carry specific genetic risk variants. Brain carriers of pathogenic mutations in APP, PSEN1 or PSEN2 presented lower neurons and higher astrocytes proportions compared to sporadic AD. Similarly, the APOE {varepsilon}4 allele also showed decreased neurons and increased astrocytes compared to AD non-carriers. On the contrary, carriers of variants in TREM2 risk showed a lower degree of neuronal loss than matched AD cases in multiple independent studies. These findings suggest that genetic risk factors associated with AD etiology have a specific imprinting in the cellular composition of AD brains. Our digital deconvolution reference panel provides an enhanced understanding of the fundamental molecular mechanisms underlying neurodegeneration, enabling the analysis of large bulk RNA-seq studies for cell composition, and suggests that correcting for the cellular structure when performing transcriptomic analysis will lead to novel insights of AD.

genetics↗