Multi-Omic Analyses of Growth Cones at Different Developmental Stages Provides Insight into Pathways in Adult Neuroregeneration.

Rabeet Fatmi,Jeffrey L Goldberg,Mohammad Samarah,Kevin K Park,Larry Benowitz,Jennifer Arcuri,Muhammad Zain Chauhan,Maroof Khan Zafar,Yuqin Yin,Sanjoy K Bhattacharya,Abigail S Hackam

doi:10.1016/j.isci.2020.100836

Abstract

SummaryGrowth cones (GCs) are structures associated with growing neurons. GC membrane expansion, which necessitates protein-lipid interactions, is critical to axonal elongation in development and in adult neuritogenesis. We present a multi-omic analysis that integrates proteomics and lipidomics data for the identification of GC pathways, cell phenotypes, and lipid-protein interactions, with an analytic platform to facilitate the visualization of these data. We combine lipidomic data from GC and adult axonal regeneration following optic nerve crush. Our results reveal significant molecular variability in GCs across developmental ages that aligns with the upregulation and downregulation of lipid metabolic processes and correlates with distinct changes in the lipid composition of GC plasmalemma. We find that these processes also define the transition into a growth-permissive state in the adult central nervous system. The insight derived from these analyses will aid in promoting adult regeneration and functional innervation in devastating neurodegenerative diseases.

Highlights

Growth cones (GCs) are terminally enlarged amoeboid-like structures of growing neurons
We present a multi-omic analysis that integrates proteomics and lipidomics data for the identification of GC pathways, cell phenotypes, and lipid-protein interactions, with an analytic platform to facilitate the visualization of these data
Our results reveal significant molecular variability in GCs across developmental ages that aligns with the upregulation and downregulation of lipid metabolic processes and correlates with distinct changes in the lipid composition of GC plasmalemma

Summary

Introduction

Growth cones (GCs) are terminally enlarged amoeboid-like structures of growing neurons They are one of a growing neuron’s most essential structures, responsible for neuronal expansion toward a target during early development, collateral sprouting resulting in additional or new neuronal connectivity, and enabling regeneration of severed neurites in the central nervous system (CNS) and peripheral nervous system (PNS) in adults. The latter is the fulcrum in devising novel intervention strategies for functional recovery in several progressive neurodegenerative diseases, such as Parkinson disease (Diaz-Martinez et al, 2013), spinal cord injuries, and progressive neuropathies, like glaucoma. These environmental cues influence axon growth and guidance by generating polarity, activating intracellular signals, and reorganizing membrane and cytoskeletal components

Objectives

Methods

Results

Discussion

Conclusion