ArticleProceedings of the National Academy of Sciences of the United States of America2014
SHP-2 deletion in postmigratory neural crest cells results in impaired cardiac sympathetic innervation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- The Loss of Tafazzin Transacetylase Activity Is Sufficient to Drive Testicular Infertility.Journal of developmental biology · 2024Article
- A Barth Syndrome Patient-DerivedInternational journal of molecular sciences · 2024Article
- Hyperactivation of MEK1 in cortical glutamatergic neurons results in projection axon deficits and aberrant motor learning.Disease models & mechanisms · 2024Article
- Shoc2 controls ERK1/2-driven neural crest development by balancing components of the extracellular matrix.Developmental biology · 2022Article
- Hyperactive MEK1 Signaling in Cortical GABAergic Neurons Promotes Embryonic Parvalbumin Neuron Loss and Defects in Behavioral Inhibition.Cerebral cortex (New York, N.Y. : 1991) · 2021Article
- Uric acid preconditioning alleviated doxorubicin induced JNK activation and Cx43 phosphorylation associated cardiotoxicity via activation of AMPK-SHP2 signaling pathway.Annals of translational medicine · 2020Article
- Analysis of UncharacterizedJournal of cardiovascular development and disease · 2019Article
- Alx4 relays sequential FGF signaling to induce lacrimal gland morphogenesis.PLoS genetics · 2017Article
- Migration pathways of sacral neural crest during development of lower urogenital tract innervation.Developmental biology · 2017Article
- Connecting teratogen-induced congenital heart defects to neural crest cells and their effect on cardiac function.Birth defects research. Part C, Embryo today : reviews · 2014Review
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6 authors.
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Abstract
Autonomic innervation is an essential component of cardiovascular regulation that is first established from the neural crest (NC) lineage in utero and continues developing postnatally. Although in vitro studies have indicated that SH2-containing protein tyrosine phosphatase 2 (SHP-2) is a signaling factor critical for regulating sympathetic neuron differentiation, this has yet to be shown in the complex in vivo environment of cardiac autonomic innervation. Targeting SHP-2 within postmigratory NC lineages resulted in a fully penetrant mouse model of diminished sympathetic cardiac innervation and concomitant bradycardia. Immunohistochemistry of the sympathetic nerve marker tyrosine hydroxylase revealed a progressive loss of adrenergic ganglionic neurons and reduction of cardiac sympathetic axon density in Shp2 cKOs. Molecularly, Shp2 cKOs exhibit lineage-specific suppression of activated phospo-ERK1/2 signaling but not of other downstream targets of SHP-2 such as pAKT. Genetic restoration of the phosphorylated-extracellular signal-regulated kinase (pERK) deficiency via lineage-specific expression of constitutively active MEK1 was sufficient to rescue the sympathetic innervation deficit and its physiological consequences. These data indicate that SHP-2 signaling specifically through pERK in postmigratory NC lineages is essential for development and maintenance of sympathetic cardiac innervation postnatally.
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