A catenin-dependent balance between N-cadherin and E-cadherin controls neuroectodermal cell fate choices

Characterizing endogenous protein expression, interaction and function, this study identifies in vivo interactions and competitive balance between N-cadherin and E-cadherin in developing avian (Gallus gallus) neural and neural crest cells. Numerous cadherin proteins, including neural cadherin (Ncad) and epithelial cadherin (Ecad), are expressed in the developing neural plate as well as in neural crest cells as they delaminate from the newly closed neural tube. To clarify independent or coordinate function during development, we examined their expression in the cranial region. The results revealed surprising overlap and distinct localization of Ecad and Ncad in the neural tube. Using a proximity ligation assay and co-immunoprecipitation, we found that Ncad and Ecad formed heterotypic complexes in the developing neural tube, and that modulation of Ncad levels led to reciprocal gain or reduction of Ecad protein, which then alters ectodermal cell fate. Here, we demonstrate that the balance of Ecad and Ncad is dependent upon the availability of β-catenin proteins, and that alteration of either classical cadherin modifies the proportions of the neural crest and neuroectodermal cells that are specified

A catenin-dependent balance between N-cadherin and E-cadherin controls neuroectodermal cell fate choices

Characterizing endogenous protein expression, interaction and function, this study identifies in vivo interactions and competitive balance between N-cadherin and E-cadherin in developing avian (Gallus gallus) neural and neural crest cells. Numerous cadherin proteins, including neural cadherin (Ncad) and epithelial cadherin (Ecad), are expressed in the developing neural plate as well as in neural crest cells as they delaminate from the newly closed neural tube. To clarify independent or coordinate function during development, we examined their expression in the cranial region. The results revealed surprising overlap and distinct localization of Ecad and Ncad in the neural tube. Using a proximity ligation assay and co-immunoprecipitation, we found that Ncad and Ecad formed heterotypic complexes in the developing neural tube, and that modulation of Ncad levels led to reciprocal gain or reduction of Ecad protein, which then alters ectodermal cell fate. Here, we demonstrate that the balance of Ecad and Ncad is dependent upon the availability of β-catenin proteins, and that alteration of either classical cadherin modifies the proportions of the neural crest and neuroectodermal cells that are specified

A catenin-dependent balance between N-cadherin and E-cadherin controls neuroectodermal cell fate choices.

Characterizing endogenous protein expression, interaction and function, this study identifies in vivo interactions and competitive balance between N-cadherin and E-cadherin in developing avian (Gallus gallus) neural and neural crest cells. Numerous cadherin proteins, including neural cadherin (Ncad) and epithelial cadherin (Ecad), are expressed in the developing neural plate as well as in neural crest cells as they delaminate from the newly closed neural tube. To clarify independent or coordinate function during development, we examined their expression in the cranial region. The results revealed surprising overlap and distinct localization of Ecad and Ncad in the neural tube. Using a proximity ligation assay and co-immunoprecipitation, we found that Ncad and Ecad formed heterotypic complexes in the developing neural tube, and that modulation of Ncad levels led to reciprocal gain or reduction of Ecad protein, which then alters ectodermal cell fate. Here, we demonstrate that the balance of Ecad and Ncad is dependent upon the availability of β-catenin proteins, and that alteration of either classical cadherin modifies the proportions of the neural crest and neuroectodermal cells that are specified

Interactions of early adversity with stress-related gene polymorphisms impact regional brain structure in females

Early adverse life events (EALs) have been associated with regional thinning of the subgenual cingulate cortex (sgACC), a brain region implicated in the development of disorders of mood and affect, and often comorbid functional pain disorders, such as irritable bowel syndrome (IBS). Regional neuroinflammation related to chronic stress system activation has been suggested as a possible mechanism underlying these neuroplastic changes. However, the interaction of genetic and environmental factors in these changes is poorly understood. The current study aimed to evaluate the interactions of EALs and candidate gene polymorphisms in influencing thickness of the sgACC. 210 female subjects (137 healthy controls; 73 IBS) were genotyped for stress and inflammation-related gene polymorphisms. Genetic variation with EALs, and diagnosis on sgACC thickness was examined, while controlling for race, age, and total brain volume. Compared to HCs, IBS had significantly reduced sgACC thickness (p = 0.03). Regardless of disease group (IBS vs. HC), thinning of the left sgACC was associated with a significant gene-gene environment interaction between the IL-1β genotype, the NR3C1 haplotype, and a history of EALs (p = 0.05). Reduced sgACC thickness in women with the minor IL-1β allele, was associated with EAL total scores regardless of NR3C1 haplotype status (p = 0.02). In subjects homozygous for the major IL-1β allele, reduced sgACC with increasing levels of EALs was seen only with the less common NR3C1 haplotype (p = 0.02). These findings support an interaction between polymorphisms related to stress and inflammation and early adverse life events in modulating a key region of the emotion arousal circuit