Work

Cerebellin-1 leads the way

Year: 2022
Type: article
Abstract: The cerebellin family of proteins influences synapse formation and function.In this issue of PLOS Biology, Han and colleagues identify a new role for Cerebellin-1 in axon growth and guidance.In development, neurons are faced with an immense challenge.As neurons grow and develop their intricate, complex shapes, they must also grow in the appropriate directions.In particular, their thin, elongated axon can travel large distances to connect with postsynaptic partners.In the past decades, the scientific community has identified an expansive catalogue of attractive and repulsive axon guidance cues that serve as road signs for the growing axon.The nature of the cues varies greatly at the molecular level-some act as soluble, chemotactic cues, while others act as adhesive, haptotactic cues.Often amplified by differentially expressed extracellular receptors and coreceptors, this vast collection of guidance cues enables different axons to navigate to precise and distinct positions in a neuron subtype-specific way.Interestingly, in recent years, a number of proteins and pathways involved in axon guidance have also been shown to be involved in the developmentally distinct process of synaptogenesis [1].This repurposing of pathways in multiple stages of development allows a limited number of genes to have multifaceted functions.Cerebellin-1 (Cbln1) was first described as a glycoprotein secreted in the cerebellum where it is required for proper synaptic function between parallel fibers and Purkinje cells [2].Notably, Cbln1 acts transAU : Pleasenotethat}trans}inthesentence}Notably; Cbln1actstrans À synaptically;-synaptically, binding both presynaptic neurexins and postsynaptic GluD2 [3].Although Cbln1 was originally thought to only play a role in the cerebellum, more recent work demonstrates that the cerebellin proteins are expressed in a variety of brain regions [4,5].For example, Cbln1 influences synapse formation in cortical and hippocampal cells [6].However, whether Cbln1 played a role during neuronal development outside of synapse organization is still unknown.In this issue of PLOS Biology, Han and colleagues report a new role for Cbln1 in axon growth and guidance [7] (Fig 1).The authors first found that Cbln1 is expressed at early stages of murine spinal cord development, well before synaptogenesis.Although Cbln1 was expressed in the spinal cord floor plate at embryonic day 10.5 (E10.5),relatively little Cbln1 was observed in the dorsal commissural neurons (DCNs) that project from one side of the spinal cord to the other.Strikingly though, they observed a rapid increase in Cbln1 expression in the DCNs from E10.5 to E12.5, overlapping with midline crossing.As this expression pattern suggested a AU : Anabbreviationlisthasbeencompiledforthoseusedthrougho potential role for Cbln1 in axon guidance, the authors used a conditional knockout (cKO) mouse to delete Cbln1 specifically in spinal cord DCNs.In vivo, DCNs lacking Cbln1 showed impeded axonal growth.Similar decreases in
Source: PLoS Biology
Language: English
Open Access status: gold
Estimated APC paid: $5,300
OpenAlex ID: W4309326575
FWCI: 0.187
Cites: 9
Cited by: 2
Related to: 10