UNC Department of Cell Biology and Physiology, 111 Mason Farm Road, Chapel Hill, NC 27599, USA.
Published: December 2015
AI Article Synopsis
Article Abstract
Neuronal growth cone filopodia contain guidance receptors and contribute to axon guidance; however, the mechanism by which the guidance cue netrin increases filopodia density is unknown. Here, we demonstrate that TRIM9, an E3 ubiquitin ligase that localizes to filopodia tips and binds the netrin receptor DCC, interacts with and ubiquitinates the barbed-end polymerase VASP to modulate filopodial stability during netrin-dependent axon guidance. Studies with murine Trim9(+/+) and Trim9(-/-) cortical neurons, along with a non-ubiquitinatable VASP mutant, demonstrate that TRIM9-mediated ubiquitination of VASP reduces VASP filopodial tip localization, VASP dynamics at tips, and filopodial stability. Upon netrin treatment, VASP is deubiquitinated, which promotes VASP tip localization and filopodial stability. Trim9 deletion induces axon guidance defects in vitro and in vivo, whereas a gradient of deubiquitinase inhibition promotes axon turning in vitro. We conclude that a gradient of TRIM9-mediated ubiquitination of VASP creates a filopodial stability gradient during axon turning.
The trigeminal ganglion is a critical structure in the peripheral nervous system, responsible for transmitting sensations of touch, pain, and temperature from craniofacial regions to the brain. Trigeminal ganglion development depends upon intrinsic cellular programming as well as extrinsic signals exchanged by diverse cell populations. With its complex anatomy and dual cellular origin from cranial placodes and neural crest cells, the trigeminal ganglion offers a rich context for examining diverse biological processes, including cell migration, fate determination, adhesion, and axon guidance.
Unlabelled: The corticospinal tract (CST) facilitates skilled, precise movements, which necessitates that subcerebral projection neurons (SCPN) establish segmentally specific connectivity with brainstem and spinal circuits. Developmental molecular delineation enables prospective identification of corticospinal neurons (CSN) projecting to thoraco-lumbar spinal segments; however, it remains unclear whether other SCPN subpopulations in developing sensorimotor cortex can be prospectively identified in this manner. Such molecular tools could enable investigations of SCPN circuitry with precision and specificity.
Critical molecular pathways promote central nervous system (CNS) axon regeneration, but can axons be guided to their correct targets in adulthood? In this issue of Developmental Cell, Delpech et al. show that axonal guidance cues in the CNS can be manipulated to enhance anatomic and functional recovery.
A deep comparative analysis of brain functional connectome across species in primates has the potential to yield valuable insights for both scientific and clinical applications. However, the interspecies commonality and differences are inherently entangled with each other and with other irrelevant factors. Here we develop a novel contrastive machine learning method, called shared-unique variation autoencoder (SU-VAE), to allow disentanglement of the species-shared and species-specific functional connectome variation between macaque and human brains on large-scale resting-state fMRI datasets.
Yak meat plays a significant economic role for yaks. The unique environment of the Qinghai-Tibet plateau profoundly impacts the meat production performance of yaks. Yet, the regulatory mechanisms influencing muscle growth and development in yaks within this plateau environment remain poorly understood.
