Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.16.2 (PCP)
 3,761 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Collective cell migration in morphogenesis and cancer progression often involves the coordination of multiple cell types. How reciprocal interactions between adjacent cell populations lead to new emergent behaviours remains unknown. Here we studied the interaction between neural crest (NC) cells, a highly migratory cell population, and placodal cells, an epithelial tissue that contributes to sensory organs. We found that NC cells chase placodal cells by chemotaxis, and placodal cells run when contacted by NC. Chemotaxis to Sdf1 underlies the chase, and repulsion involving PCP and N-cadherin signalling is responsible for the run. This chase-and-run requires the generation of asymmetric forces, which depend on local inhibition of focal adhesions. The cell interactions described here are essential for correct NC migration and for segregation of placodes in vivo and are likely to represent a general mechanism of coordinated migration.
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PMID:Chase-and-run between adjacent cell populations promotes directional collective migration. 2382 Jul 41

The neural crest-a key innovation of the vertebrates-gives rise to diverse cell types including melanocytes, neurons and glia of the peripheral nervous system, and chondrocytes of the jaw and skull. Proper development of the cephalic region is dependent on the tightly-regulated specification and migration of cranial neural crest cells (NCCs). The core PCP proteins Frizzled and Disheveled have previously been implicated in NCC migration. Here we investigate the functions of the core PCP proteins Prickle1a and Prickle1b in zebrafish cranial NCC development. Using analysis of pk1a and pk1b mutant embryos, we uncover similar roles for both genes in facilitating cranial NCC migration. Disruption of either gene causes pre-migratory NCCs to cluster together at the dorsal aspect of the neural tube, where they adopt aberrant polarity and movement. Critically, in investigating Pk1-deficient cells that fail to migrate ventrolaterally, we have also uncovered roles for pk1a and pk1b in the epithelial-to-mesenchymal transition (EMT) of pre-migratory NCCs that precedes their collective migration to the periphery. Normally, during EMT, pre-migratory NCCs transition from a neuroepithelial to a bleb-based and subsequently, mesenchymal morphology capable of directed migration. When either Pk1a or Pk1b is disrupted, NCCs continue to perform blebbing behaviors characteristic of pre-migratory cells over extended time periods, indicating a block in a key transition during EMT. Although some Pk1-deficient NCCs transition successfully to mesenchymal, migratory morphologies, they fail to separate from neighboring NCCs. Additionally, Pk1b-deficient NCCs show elevated levels of E-Cadherin and reduced levels of N-Cadherin, suggesting that Prickle1 molecules regulate Cadherin levels to ensure the completion of EMT and the commencement of cranial NCC migration. We conclude that Pk1 plays crucial roles in cranial NCCs both during EMT and migration. These roles are dependent on the regulation of E-Cad and N-Cad.
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PMID:Prickle1 is required for EMT and migration of zebrafish cranial neural crest. 3072 65

Adolescent neurodevelopment confer vulnerability to the actions of treatments that produce adaptations in neurocircuitry underlying motivation, impulsivity and reward. Considering wide usage of a sedative-hypnotic agent propofol in clinical practice, we examined whether propofol is a challenging treatment for peripubertal brain. Motivation/hedonic behavior (sucrose preference test), approach/avoidance behavior (elevated plus maze test) and response to dissociative drug phencyclidine (PCP) were studied in peripubertal rats (the rodent model of periadolescence) after propofol anesthesia exposure (PAE). Neurodegeneration (Fluoro-Jade staining) and the expression of proteins (Western blot) involved in excitatory synaptic transmission and activity-dependent synaptic stabilization in the medial prefrontal cortex (mPFC) and striatum (components of motivation/reward circuitry; process both appetitive and aversive events) were examined as well. In peripubertal rats PAE produced 1) transient brain-region specific changes in the expression of N-methyl-d-aspartate (NMDA) receptor subunits NR2A and NR2B, PSD-95 and N-cadherin, without neurotoxicity, 2) hyperlocomotor response to PCP, 3) no changes in preference for palatable 1% sucrose solution and a decrease in food eaten, 4) preference for 20% sucrose solution without changes in food eaten, 5) stretch-attended postures and open arms entries in the elevated plus maze test. Overall, these novel findings show that PAE leaves transient synaptic trace recognized as early form of synaptic plasticity related to passive drug exposure in the brain systems implicated in motivation/reward, increases drug-responsiveness, favors risk-taking and preference of novel/intense stimuli repairing otherwise present motivational deficiency. These findings accentuate multifaceted response to propofol in peripuberty and the importance of environmental stability for the most favorable neurobehavioral recovery.
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PMID:Motivation, risk-taking and sensation seeking behavior in propofol anesthesia exposed peripubertal rats. 3141 78