scholarly journals Functional divergence of Plexin B structural motifs in distinct steps ofDrosophilaolfactory circuit assembly

2019 ◽  
Author(s):  
Ricardo Guajardo ◽  
David J Luginbuhl ◽  
Shuo Han ◽  
Liqun Luo ◽  
Jiefu Li
Keyword(s):  
Neural Development ◽  
Neural Circuit ◽  
Functional Divergence ◽  
Partner Selection ◽  
Structural Motifs ◽  
Binding Motifs ◽  
Sema Domain ◽  
Stepwise Assembly ◽  
Circuit Assembly

AbstractPlexins exhibit multitudinous, evolutionarily conserved functions in the development of nervous systems. However, how Plexins employ their diverse structural motifsin vivoto perform distinct roles in the stepwise assembly of neural circuits is unclear. Here, we systematically mutagenized structural motifs ofDrosophilaPlexin B (PlexB) and examined the function of these variants at multiple PlexB-mediated neurodevelopmental processes in olfactory receptor neurons: axon fasciculation, trajectory choice, and synaptic partner selection. We found that the extracellular Sema domain is essential for all three processes, the catalytic site of the intracellular RapGAP is engaged in none, and the intracellular GTPase-binding motifs are essential for trajectory choice and synaptic partner selection, but are dispensable for fasciculation. Moreover, extracellular PlexB cleavage serves as a regulatory mechanism of PlexB signaling. Thus, PlexB structural motifs have divergent roles in distinct steps of neural development, altogether contributing to the functional versatility of PlexB in neural circuit assembly.

scholarly journals Functional divergence of Plexin B structural motifs in distinct steps of Drosophila olfactory circuit assembly

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Ricardo Guajardo ◽  
David J Luginbuhl ◽  
Shuo Han ◽  
Liqun Luo ◽  
Jiefu Li
Keyword(s):  
Neural Development ◽  
Neural Circuit ◽  
Functional Divergence ◽  
Partner Selection ◽  
Structural Motifs ◽  
Binding Motifs ◽  
Sema Domain ◽  
Evolutionarily Conserved ◽  
Circuit Assembly

Plexins exhibit multitudinous, evolutionarily conserved functions in neural development. How Plexins employ their diverse structural motifs in vivo to perform distinct roles is unclear. We previously reported that Plexin B (PlexB) controls multiple steps during the assembly of the Drosophila olfactory circuit (Li et al., 2018b). Here, we systematically mutagenized structural motifs of PlexB and examined the function of these variants in these multiple steps: axon fasciculation, trajectory choice, and synaptic partner selection. We found that the extracellular Sema domain is essential for all three steps, the catalytic site of the intracellular RapGAP is engaged in none, and the intracellular GTPase-binding motifs are essential for trajectory choice and synaptic partner selection, but are dispensable for fasciculation. Moreover, extracellular PlexB cleavage serves as a regulatory mechanism of PlexB signaling. Thus, the divergent roles of PlexB motifs in distinct steps of neural development contribute to its functional versatility in neural circuit assembly.

scholarly journals Cell-Surface Proteomic Profiling in the Fly Brain Uncovers New Wiring Regulators

2019 ◽  
Author(s):  
Jiefu Li ◽  
Shuo Han ◽  
Hongjie Li ◽  
Namrata D. Udeshi ◽  
Tanya Svinkina ◽  
...  
Keyword(s):  
Cell Surface ◽  
Neural Development ◽  
Neural Circuit ◽  
Single Cells ◽  
Projection Neurons ◽  
Proteomic Profiling ◽  
A Cell ◽  
Cell Type Specific ◽  
Multicellular Organisms

SUMMARYMolecular interactions at the cellular interface mediate organized assembly of single cells into tissues, and thus govern the development and physiology of multicellular organisms. Here, we developed a cell-type-specific, spatiotemporally-resolved approach to profile cell-surface proteomes in intact tissues. Quantitative profiling of cell-surface proteomes of Drosophila olfactory projection neurons (PNs) in pupae and adults revealed a global down-regulation of wiring molecules and an up-regulation of synaptic molecules in the transition from developing to mature PNs. A proteome-instructed in vivo screen identified 20 new cell-surface molecules regulating neural circuit assembly, many of which belong to evolutionarily conserved protein families not previously linked to neural development. Genetic analysis further revealed that the lipoprotein receptor LRP1 cell-autonomously controls PN dendrite targeting, contributing to the formation of a precise olfactory map. These findings highlight the power of temporally-resolved in situ cell-surface proteomic profiling in discovering new regulators of brain wiring.

scholarly journals Architects in neural circuit design: Glia control neuron numbers and connectivity

2013 ◽  
Vol 203 (3) ◽  
pp. 395-405 ◽  
Author(s):  
Megan M. Corty ◽  
Marc R. Freeman
Keyword(s):  
Nervous System ◽  
Circuit Design ◽  
Glial Cells ◽  
Neural Development ◽  
Molecular Mechanisms ◽  
Neural Circuit ◽  
Neuronal Circuit ◽  
Circuit Formation

Glia serve many important functions in the mature nervous system. In addition, these diverse cells have emerged as essential participants in nearly all aspects of neural development. Improved techniques to study neurons in the absence of glia, and to visualize and manipulate glia in vivo, have greatly expanded our knowledge of glial biology and neuron–glia interactions during development. Exciting studies in the last decade have begun to identify the cellular and molecular mechanisms by which glia exert control over neuronal circuit formation. Recent findings illustrate the importance of glial cells in shaping the nervous system by controlling the number and connectivity of neurons.

scholarly journals Distributed processing for action control by prelimbic circuits targeting anterior-posterior dorsal striatal subregions.

2021 ◽  
Author(s):  
Kyuhyun Choi ◽  
Eugenio Piasini ◽  
Luigim Cifuentes Vargas ◽  
Nathan T Henderson ◽  
Edgar Diaz Hernandez ◽  
...  
Keyword(s):  
Functional Diversity ◽  
Neural Circuit ◽  
Single Photon ◽  
Functional Divergence ◽  
Distributed Processing ◽  
Action Control ◽  
Positive Outcomes ◽  
Negative Outcomes ◽  
Anterior Posterior

Fronto-striatal circuits have been extensively implicated in the cognitive control of behavioral output for both social and appetitive rewards. The functional diversity of prefrontal cortical populations is strongly dependent on their synaptic targets, with control of motor output strongly mediated by connectivity to the dorsal striatum. Despite evidence for functional diversity along the anterior-posterior axis of the dorsomedial striatum (DMS), it is unclear how distinct fronto-striatal sub-circuits support neural computations essential for action selection. Here we identify prefrontal populations targeting distinct DMS subregions and characterize their functional roles. We first performed neural circuit tracing to reveal segregated prefrontal populations defined by anterior/posterior dorsomedial striatal target. We then probed the functional relevance of these parallel circuits via in vivo calcium imaging and temporally precise causal manipulations during a feedback-based 2-alternative choice task. Single-photon imaging revealed circuit-specific representations of task-relevant information with prelimbic neurons targeting anterior DMS (PL::A-DMS) uniquely encoded choices and responses to negative outcomes, while prelimbic neurons targeting posterior DMS (PL::P-DMS) encoded internal representations of value and positive outcomes contingent on prior choice. Consistent with this distributed coding, optogenetic inhibition of PL::A-DMS circuits strongly impacted choice monitoring and behavioral control in response to negative outcomes while perturbation of PL::P-DMS signals impaired task engagement and strategies following positive outcomes. Di-synaptic retrograde tracing uncovered differences in afferent connectivity that may underlie these pathways functional divergence. Together our data uncover novel PL populations engaged in distributed processing for action control.

Barcoded Rational AAV Vector Evolution Enables Systematic In Vivo Mapping of Peptide Binding Motifs

2018 ◽  
Author(s):  
Marcus Davidsson ◽  
Gang Wang ◽  
Patrick Aldrin-Kirk ◽  
Tiago Cardoso ◽  
Sara Nolbrant ◽  
...  
Keyword(s):  
Peptide Binding ◽  
Aav Vector ◽  
Binding Motifs

scholarly journals Rgs4 is a regulator of mTOR activity required for motoneuron axon outgrowth and neuronal development in zebrafish

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Aya Mikdache ◽  
Marie-José Boueid ◽  
Lorijn van der Spek ◽  
Emilie Lesport ◽  
Brigitte Delespierre ◽  
...  
Keyword(s):  
Nervous System ◽  
G Protein ◽  
Neural Development ◽  
Neuronal Development ◽  
Axon Outgrowth ◽  
Rgs Proteins ◽  
Protein Signaling ◽  
Loss Of Function ◽  
G Protein Coupled

AbstractThe Regulator of G protein signaling 4 (Rgs4) is a member of the RGS proteins superfamily that modulates the activity of G-protein coupled receptors. It is mainly expressed in the nervous system and is linked to several neuronal signaling pathways; however, its role in neural development in vivo remains inconclusive. Here, we generated and characterized a rgs4 loss of function model (MZrgs4) in zebrafish. MZrgs4 embryos showed motility defects and presented reduced head and eye sizes, reflecting defective motoneurons axon outgrowth and a significant decrease in the number of neurons in the central and peripheral nervous system. Forcing the expression of Rgs4 specifically within motoneurons rescued their early defective outgrowth in MZrgs4 embryos, indicating an autonomous role for Rgs4 in motoneurons. We also analyzed the role of Akt, Erk and mechanistic target of rapamycin (mTOR) signaling cascades and showed a requirement for these pathways in motoneurons axon outgrowth and neuronal development. Drawing on pharmacological and rescue experiments in MZrgs4, we provide evidence that Rgs4 facilitates signaling mediated by Akt, Erk and mTOR in order to drive axon outgrowth in motoneurons and regulate neuronal numbers.

scholarly journals PGC7 suppresses TET3 for protecting DNA methylation

2013 ◽  
Vol 42 (5) ◽  
pp. 2893-2905 ◽  
Author(s):  
Chunjing Bian ◽  
Xiaochun Yu
Keyword(s):  
Dna Methylation ◽  
Molecular Mechanism ◽  
Biological Process ◽  
Cpg Islands ◽  
Binding Motifs ◽  
Genome Wide Analysis ◽  
Dna Motif ◽  
Genome Wide

Abstract Ten-eleven translocation (TET) family enzymes convert 5-methylcytosine to 5-hydroxylmethylcytosine. However, the molecular mechanism that regulates this biological process is not clear. Here, we show the evidence that PGC7 (also known as Dppa3 or Stella) interacts with TET2 and TET3 both in vitro and in vivo to suppress the enzymatic activity of TET2 and TET3. Moreover, lacking PGC7 induces the loss of DNA methylation at imprinting loci. Genome-wide analysis of PGC7 reveals a consensus DNA motif that is recognized by PGC7. The CpG islands surrounding the PGC7-binding motifs are hypermethylated. Taken together, our study demonstrates a molecular mechanism by which PGC7 protects DNA methylation from TET family enzyme-dependent oxidation.

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