Axons

Brain tissue comprises an extremely complex arrangement of cells that together make up the information- processing network enabling brain function. The connectivity of neurons underlies the unparalleled capabilities of our mind. Thus, mapping brain structure, which underlies brain function, has become a central focus in neuroscience.Electron microscopy provides extremely high resolution and comprehensive visualization of brain structure but requires correlative workflows to access molecular information. Light microscopy holds tremendous potential to analyze the ultrastructure of brain tissue t

…mRNA transport to dendrites and axons and local translation are crucial for development, repair, synaptic function and memory formation.3’ untranslated regions (3’UTRs) are known for regulation of RNA localization, stability and translation. Past research identified many of the molecular mechanisms and players involved, but we still lack a systematic understanding of how the regulatory information is encoded i

…Axons, in particular, have unipolarized microtubules with the plus ends growing away from the soma. This leads to an aligned microtubule organization in

The actin cytoskeleton is a key component for neuronal architecture and function. Along the axon, actin filaments assemble into distinct subcellular structures in the initial segment, along the distal shaft and within presynaptic boutons. Despite advances in the field of super-resolution microscopy, little is known about the presynaptic actin cytoskeleton, because of difficulties in visualizing it alongside the highly enriched postsynaptic compartment.Our objective is to map the presynaptic actin cytoskeleton scaffold and identify its nanostructures to further understand its functions. We have

…ribosomes, within dendrites and axons. Local translation of mRNAs is important for the function and plasticity of synapses. Using advanced sequencing and imaging techniques we have updated our understanding of the local transcriptome and identified the local translatome- identifying over 800 transcripts for which local translation is the dominant source of protein. In addition, we have explored the unique mechanisms neur

…by splicing proteins in developing axons.

…and processes within dendrites and axons. Using expansion microscopy together with metabolic labeling we have discovered that both postsynaptic spines and presynaptic terminals exhibit rapid translation, which exhibits differential sensitivity to different neurotransmitters and neuromodulators. In addition, we have explored the unique mechanisms neurons use to meet protein demands at synapses, identifying the transcriptome and transla

Axons degenerate before the neuronal soma in many neurodegenerative diseases. Programmed axon death (Wallerian degeneration) is a widely-occurring mechanism of axon loss that is well understood and preventable in animals. Its aberrant activation by mutation of the pro-survival gene Nmnat2 directly causes axonopathy in mice with severity ranging from mild polyneuropathy to perinatal lethality. Rare biallelic mutations in the homologous human gene cause related phenotypes in patients. NMNAT2 is a negative regulator of the prodegenerative NADase SARM1. Constitutive activation of SARM1 is cytotoxi