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The axons of retinal ganglion cells (RGCs) are topographically sorted before they arrive at the optic tectum. This pre-target sorting, typical of axon tracts throughout the brain, is poorly understood. Here, we show that cytoplasmic FMR1-interacting proteins (CYFIPs) fulfill non-redundant functions in RGCs, with CYFIP1 mediating axon growth and CYFIP2 specifically involved in axon sorting. We find that CYFIP2 mediates homotypic and heterotypic contact-triggered fasciculation and repulsion responses between dorsal and ventral axons. CYFIP2 associates with transporting ribonucleoprotein particles in axons and regulates translation. Axon-axon contact stimulates CYFIP2 to move into growth cones where it joins the actin nucleating WAVE regulatory complex (WRC) in the periphery and regulates actin remodeling and filopodial dynamics. CYFIP2's function in axon sorting is mediated by its binding to the WRC but not its translational regulation. Together, these findings uncover CYFIP2 as a key regulatory link between axon-axon interactions, filopodial dynamics, and optic tract sorting.
This article was published in the following journal.
In the developing visual system, retinal ganglion cell (RGC) axons project from the retina to several distal retinorecipient regions in the brain. Several molecules have been implicated in guiding RGC...
RNA-binding proteins Lin28a/b regulate cellular growth and tissue regeneration. Here, we investigated the role of Lin28 in the control of axon regeneration in postmitotic neurons. We find that Lin28a/...
Neurons are capable of degenerating their axons for the physiological clearance and refinement of unnecessary connections via the programmed degenerative pathways of apoptosis and axon pruning. While ...
This review addresses issues relating to the survival and axon regeneration of both intrinsically photosensitive retinal ganglion cells (ipRGC) and αRGC, and possible ensuing patterns of functional r...
The failure of mature central nervous system (CNS) projection neurons to regenerate axons over long distances drastically limits the recovery of functions lost after various CNS injuries and diseases....
Cervical myelopathy (CM), a chronically compressive spinal cord lesion, is the most common cause of non-traumatic paraparesis/quadriparesis among the elderly. Hong Kong is facing a heavy s...
In Parkinson's disease (PD), alpha-synuclein accumulation in cutaneous autonomic pilomotor and sudomotor nerve fibers has been linked to autonomic nervous system disturbances even in the e...
This study analyzed diabetic patients without evidence of glaucoma who underwent panretinal photocoagulation to determine the effect on optic disc topographic parameters in non-glaucomatou...
Autonomic Profiles in Pediatric Patients With Cyclic Vomiting Syndrome (CVS), Irritable Bowel Syndrome (IBS),Postural Orthostatic Tachycardia Syndrome (POTS), Functional Abdominal Pain (FAP) or Chronic Nausea
Retrospectively review the charts of all children who had heart rate variability, deep breathing test, valsalva maneuver, tilt table test, thermoregulatory sweat testing, quantitative sudo...
Non-arthritic anterior ischemic optic neuropathy is the most common cause of sudden visual loss due to optic nerve involvement in patients above 50 years old. As this problem can be consid...
First segment of axon that connects distal axon segments to the neuronal CELL BODY at the axon hillock region. The axon initial segment is not protected by the MYELIN SHEATH and has properties critical for axonal growth. The axon initial segment and the axon hillock form an axonal trigger zone.
Degeneration of distal aspects of a nerve axon following injury to the cell body or proximal portion of the axon. The process is characterized by fragmentation of the axon and its MYELIN SHEATH.
A contactin subtype that plays a role in axon outgrowth, axon fasciculation, and neuronal migration.
The mechanism by which a neuronal process outgrows toward a target led by the GROWTH CONE. Local guidance cues are provided by cell surface proteins that act on the growing axon.
A receptor for NETRIN-1 that contains four membrane distal (N-terminal) Ig-like C2 domains and six membrane proximal (C-terminal) fibronectin type III domains. It is expressed primarily in the nerve axons and differentiated intestinal cells and is required for AXON GUIDANCE, mediating axon attraction of neuronal GROWTH CONES; however, it may also trigger axon repulsion through association with the UNC5 netrin-1 receptor. DCC also induces APOPTOSIS when it is unbound from netrin-1. Deletions of the DCC gene are observed in tumor metastases and the protein is not expressed in undifferentiated COLORECTAL CARCINOMA cells.