UNC-16 interacts with LRK-1 and WDFY-3 to regulate the termination of axon growth.

In humans, MAPK8IP3 (also known as JIP3) is a neurodevelopmental disorder-associated gene. In Caenorhabditis elegans, the UNC-16 ortholog of the MAPK8IP3 protein can regulate the termination of axon growth. However, its role in this process is not well understood.

UNC-16 interacts with LRK-1 and WDFY-3 to regulate the termination of axon growth.

is a neurodevelopmental-disorder associated gene that can regulate the termination of axon growth. However, its role in this process is not well understood. Here, we report that UNC-16 promotes axon termination through a process that includes the LRK-1(LRRK-1/LRRK-2) kinase and the WDFY-3 (WDFY3/Alfy) selective autophagy protein.

Autism candidate gene () regulates MALS-1 to protect against mitochondrial dysfunction and axon degeneration during neurodevelopment.

Mitochondrial dysfunction is thought to be a key component of neurodevelopmental disorders such as autism, intellectual disability, and ADHD. However, little is known about the molecular mechanisms that protect against mitochondrial dysfunction during neurodevelopment. Here, we address this question through the investigation of , the ortholog of the autism candidate gene, which encodes an RNA-binding protein whose role in neurons is unknown.

UNC-116 and UNC-16 function with the NEKL-3 kinase to promote axon targeting.

KIF5C is a kinesin-1 heavy chain that has been associated with neurodevelopmental disorders. Although the roles of kinesin-1 in axon transport are well known, little is known about how it regulates axon targeting. We report that UNC-116/KIF5C functions with the NEKL-3/NEK6/7 kinase to promote axon targeting in Caenorhabditis elegans.

The ANC-1 (Nesprin-1/2) organelle-anchoring protein functions through mitochondria to polarize axon growth in response to SLT-1.

A family of giant KASH proteins, including C. elegans ANC-1 and mammalian Nesprin-1 and -2, are involved in organelle anchoring and are associated with multiple neurodevelopmental disorders including autism, bipolar disorder, and schizophrenia. However, little is known about how these proteins function in neurons.

An autism-associated calcium channel variant causes defects in neuronal polarity in the ALM neuron of .

Variants of the voltage-gated calcium channel gene have been associated with autism and other neurodevelopmental disorders including bipolar disorder, schizophrenia, and ADHD. The Timothy syndrome mutation is a rare gain-of-function variant in that causes autism with high penetrance, providing a powerful avenue into investigating the role of variants in neurodevelopmental disorders. In our previous work, we demonstrated that an mutation, which is equivalent to the Timothy syndrome mutation in can disrupt termination of the PLM axon in .

An autism-causing calcium channel variant functions with selective autophagy to alter axon targeting and behavior.

Common and rare variants of the CACNA1C voltage-gated calcium channel gene have been associated with autism and other neurodevelopmental disorders including schizophrenia, bipolar disorder and ADHD. However, little is known about how CACNA1C variants affect cellular processes to alter neurodevelopment. The Timothy syndrome mutation is a rare de novo gain-of-function variant in CACNA1C that causes autism with high penetrance, providing a powerful avenue into investigating the role of CACNA1C variants in neurodevelopmental disorders.

Transition between synaptic branch formation and synaptogenesis is regulated by the lin-4 microRNA.

Axonal branch formation and synaptogenesis are sequential events that are required for the establishment of neuronal connectivity. However, little is known about how the transition between these two events is regulated. Here, we report that the lin-4 microRNA can regulate the transition between branch formation and synaptogenesis in the PLM axon of C.

SYD-1 Promotes Multiple Developmental Steps Leading to Neuronal Connectivity.

The establishment of neuronal connectivity requires precise orchestration of multiple developmental steps, including axon specification, axon guidance, selection of synaptic target sites, and development of synaptic specializations. Although these are separate developmental steps, evidence indicates that some of the signaling molecules that regulate these steps are shared. In this review, we focus on SYD-1, a RhoGAP-like protein that has been implicated in each step of axonal development.

SYD-1C, UNC-40 (DCC) and SAX-3 (Robo) function interdependently to promote axon guidance by regulating the MIG-2 GTPase.

During development, axons must integrate directional information encoded by multiple guidance cues and their receptors. Axon guidance receptors, such as UNC-40 (DCC) and SAX-3 (Robo), can function individually or combinatorially with other guidance receptors to regulate downstream effectors. However, little is known about the molecular mechanisms that mediate combinatorial guidance receptor signaling.

MIG-10 functions with ABI-1 to mediate the UNC-6 and SLT-1 axon guidance signaling pathways.

Extracellular guidance cues steer axons towards their targets by eliciting morphological changes in the growth cone. A key part of this process is the asymmetric recruitment of the cytoplasmic scaffolding protein MIG-10 (lamellipodin). MIG-10 is thought to asymmetrically promote outgrowth by inducing actin polymerization.

Axon response to guidance cues is stimulated by acetylcholine in Caenorhabditis elegans.

Gradients of acetylcholine can stimulate growth cone turning when applied to neurons grown in culture, and it has been suggested that acetylcholine could act as a guidance cue. However, the role acetylcholine plays in directing axon migrations in vivo is not clear. Here, we show that acetylcholine positively regulates signaling pathways that mediate axon responses to guidance cues in Caenorhabditis elegans.

Axon guidance: asymmetric signaling orients polarized outgrowth.

A network of connections is established as neural circuits form between neurons. To make these connections, neurons initiate asymmetric axon outgrowth in response to extracellular guidance cues. Within the specialized growth cones of migrating axons, F-actin and microtubules asymmetrically accumulate where an axon projects forward.

CED-10/Rac1 mediates axon guidance by regulating the asymmetric distribution of MIG-10/lamellipodin.

Axon migrations are guided by extracellular cues that induce asymmetric outgrowth activity in the growth cone. Several intracellular signaling proteins have been implicated in the guidance response. However, how these proteins interact to generate asymmetric outgrowth activity is unknown.

Axon guidance: ephrins at WRK on the midline.

Recent findings indicate that the embryonic motor neurons act as gatekeepers to regulate midline crossing during development of the nematode Caenorhabditis elegans. The newly identified protein WRK-1 and ephrins cooperate to prevent longitudinal axons from crossing the midline.

UNC-6/netrin and SLT-1/slit guidance cues orient axon outgrowth mediated by MIG-10/RIAM/lamellipodin.

Background: Axon migrations are guided by extracellular cues that can act as repellants or attractants. However, the logic underlying the manner through which attractive and repulsive responses are determined is unclear. Many extracellular guidance cues, and the cellular components that mediate their signals, have been implicated in both types of responses.

TUC-4b, a novel TUC family variant, regulates neurite outgrowth and associates with vesicles in the growth cone.

The TUC (TOAD-64/Ulip/CRMP) proteins are homologs of UNC-33, a protein that is required for axon extension and guidance in Caenorhabditis elegans. The TUC proteins are expressed in newly born neurons in the developing nervous system and have been implicated in semaphorin signaling and neuronal polarity. Here, we identify several new variants of the TUC family, each of which is expressed during distinct periods of neural development.

Differential proteome analysis of replicative senescence in rat embryo fibroblasts.

Normal somatic cells undergo a finite number of divisions and then cease dividing whereas cancer cells are able to proliferate indefinitely. To identify the underlying mechanisms that limit the mitotic potential, a two-dimensional differential proteome analysis of replicative senescence in serially passaged rat embryo fibroblasts was undertaken. Triplicate independent two-dimensional gels containing over 1200 spots each were run, curated, and analyzed.