Hoxa3Cre-driven deletion of Pcsk5. Ethidium bromide stained agarose gel showing multiplex polymerase chain reaction products of allele-specific genotyping from embryonic hearts. Primer details are as in Fig.Â 5. Five hearts of the Pcsk5 Î1/flox ; Hoxa3Cre + embryos were analysed. The floxed allele is almost completely absent in this hearts indicating a loss of Pcsk5 floxed allele. (TIF 477Â kb

Angela Keeling (3964229)

Annik Prat (148078)

Dorota Szumska (246891)

Milena Cioroch (3964226)

Nabil Seidah (71918)

Shoumo Bhattacharya (126386)

BMC Developmental Biology

Dorota Szumska

Milena Cioroch

Angela Keeling

Annik Prat

Nabil G. Seidah

Shoumo Bhattacharya

Crossref

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

Background Loss of proprotein convertase subtilisin/kexin type 5 (Pcsk5) results in multiple developmental anomaliesincluding 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). Results Using 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. Conclusions Our 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

Szumska, Dorota

Cioroch, Milena

Keeling, A

Prat, A

Seidah, NG

Bhattacharya, Shoumo

ORA - Oxford University Research Archive

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

Oxford University Research Archive

English

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Additional file 1: Figure S1. of 
                     Pcsk5 is required in the early cranio-cardiac mesoderm for heart development

Background
Loss of proprotein convertase subtilisin/kexin type 5 (Pcsk5) results in multiple developmental anomaliesincluding 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 and Radial anomalies and Limb defects).
Results
Using 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.
Conclusions
Our 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.</p

Szumska, D

Cioroch, M

Bhattacharya, S

Oxford University Research Archive (ORA)

https://figshare.com/articles/Additional_file_1_Figure_S1_of___Pcsk5_is_required_in_the_early_cranio-cardiac_mesoderm_for_heart_development/4923452

Additional file 1: Figure S1. of Pcsk5 is required in the early cranio-cardiac mesoderm for heart development

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ORA - Oxford University Research Archive

Oxford University Research Archive

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Oxford University Research Archive (ORA)