Pcsk5 is required in the early cranio-cardiac mesoderm for heart development

Abstract

BackgroundLoss of proprotein convertase subtilisin/kexin type 5 (Pcsk5) results in multiple developmental anomalies including cardiac malformations, caudal regression, pre-sacral mass, renal agenesis, anteroposterior patterning defects, and tracheo-oesophageal and anorectal malformations, and is a model for VACTERL/caudal regression/Currarino syndromes (VACTERL association - Vertebral anomalies, Anal atresia, Cardiac defects, Tracheoesophageal fistula and/or Esophageal atresia, Renal & Radial anomalies and Limb defects).ResultsUsing magnetic resonance imaging (MRI), we examined heart development in mouse embryos with zygotic and cardiac specific deletion of Pcsk5. We show that conditional deletion of Pcsk5 in all epiblastic lineages recapitulates all developmental malformations except for tracheo-esophageal malformations. Using a conditional deletion strategy, we find that there is an essential and specific requirement for Pcsk5 in the cranio-cardiac mesoderm for cardiogenesis, but not for conotruncal septation or any other aspect of embryonic development. Surprisingly, deletion of Pcsk5 in cardiogenic or pharyngeal mesodermal progenitors that form later from the cranio-cardiac mesoderm does not affect heart development. Neither is Pcsk5 essential in the neural crest, which drives conotruncal septation.ConclusionsOur results suggest that Pcsk5 may have an essential and early role in the cranio-cardiac mesoderm for heart development. Alternatively, it is possible that Pcsk5 may still play a critical role in Nkx2.5-expressing cardiac progenitors, with persistence of mRNA or protein accounting for the lack of effect of deletion on heart development.Electronic supplementary materialThe online version of this article (doi:10.1186/s12861-017-0148-y) contains supplementary material, which is available to authorized users.

Genetic Alterations in Papillary Thyroid Carcinoma With Hashimoto’s Thyroiditis： ANK3, an Indolent Maintainer of Papillary Thyroid Carcinoma

“…The next significant SMG was PCSK5 (six samples), but its function has not yet been fully elucidated. Several reports revealed that PCSK5 is involved in the development of embryos ( 36 , 37 ), whereas only few evidences have confirmed that PCSK5 is associated with cancer ( 38 ).…”

Selective inhibition of N-linked glycosylation impairs receptor tyrosine kinase processing

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Therapeutic potential of the Proprotein Convertase Subtilisin/Kexin family in vascular disease

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