Imprinted Gene Expression and Function of the Dopa Decarboxylase Gene in the Developing Heart

Adam R. Prickett; Bertille Montibus; Nikolaos Barkas; Samuele M. Amante; Maurício M. Franco; Michael Cowley; William Puszyk; Matthew F. Shannon; Melita D. Irving; Marta Madon-Simon; Andrew Ward; Reiner Schulz; H. Scott Baldwin; Rebecca J. Oakey

doi:10.3389/fcell.2021.676543

Imprinted Gene Expression and Function of the Dopa Decarboxylase Gene in the Developing Heart

Adam R. Prickett, Bertille Montibus, Nikolaos Barkas, Samuele M. Amante, Maurício M. Franco, Michael Cowley, William Puszyk, Matthew F. Shannon, Melita D. Irving, Marta Madon-Simon, Andrew Ward, Reiner Schulz, H. Scott Baldwin, Rebecca J. Oakey

Department of Life Sciences

Research output: Contribution to journal › Article › peer-review

7 Citations (SciVal)

Abstract

Dopa decarboxylase (DDC) synthesizes serotonin in the developing mouse heart where it is encoded by Ddc_exon1a, a tissue-specific paternally expressed imprinted gene. Ddc_exon1a shares an imprinting control region (ICR) with the imprinted, maternally expressed (outside of the central nervous system) Grb10 gene on mouse chromosome 11, but little else is known about the tissue-specific imprinted expression of Ddc_exon1a. Fluorescent immunostaining localizes DDC to the developing myocardium in the pre-natal mouse heart, in a region susceptible to abnormal development and implicated in congenital heart defects in human. Ddc_exon1a and Grb10 are not co-expressed in heart nor in brain where Grb10 is also paternally expressed, despite sharing an ICR, indicating they are mechanistically linked by their shared ICR but not by Grb10 gene expression. Evidence from a Ddc_exon1a gene knockout mouse model suggests that it mediates the growth of the developing myocardium and a thinning of the myocardium is observed in a small number of mutant mice examined, with changes in gene expression detected by microarray analysis. Comparative studies in the human developing heart reveal a paternal expression bias with polymorphic imprinting patterns between individual human hearts at DDC_EXON1a, a finding consistent with other imprinted genes in human.

Original language	English
Article number	676543
Journal	Frontiers in Cell and Developmental Biology
Volume	9
DOIs	https://doi.org/10.3389/fcell.2021.676543
Publication status	Published - 22 Jun 2021

Bibliographical note

Funding Information:
We thank Dr. Matt Arno and the KCL genomics facility for core equipment usage. We acknowledge support from the Department of Health via the National Institute for Health Research (NIHR) Biomedical Research Centre at Guy?s and St Thomas? NHS Foundation Trust in partnership with King?s College London for access to the genomics core facility at the time directed by Dr. Alka Saxena. We thank James Cain for help with the figures, Dr. Heba Saadeh for assistance with bioinformatics analysis of the expression microarray and Dr. Sabrina B?hm for technical support. We thank the MRC-Wellcome Trust Human Developmental Biology Resource (HDBR) (http://www.hdbr.org) from the Institute of Genetic Medicine, Newcastle and Institute of Child Health, London for human fetal tissues. Funding. This work was supported by the British Heart Foundation Project Grant (PG/13/35/30236) (RO) and PhD studentship FS/08/051/25748 (to RO undertaken by AP), the Wellcome Trust Project Grant (084358/Z/07/Z) (RO), the Medical Research Council Project Grant (G1001689) (RO), the National Institutes of Health (1R01 HL118386) (HB), and EFIC facility, the National Institute of Health (S10-RR27661) (HB).

Keywords

dopa decarboxylase
heart
human
imprinting
knock-out
mouse

ASJC Scopus subject areas

Developmental Biology
Cell Biology

Access to Document

10.3389/fcell.2021.676543Licence: CC BY

Cite this

Prickett, A. R., Montibus, B., Barkas, N., Amante, S. M., Franco, M. M., Cowley, M., Puszyk, W., Shannon, M. F., Irving, M. D., Madon-Simon, M., Ward, A., Schulz, R., Baldwin, H. S., & Oakey, R. J. (2021). Imprinted Gene Expression and Function of the Dopa Decarboxylase Gene in the Developing Heart. Frontiers in Cell and Developmental Biology, 9, Article 676543. https://doi.org/10.3389/fcell.2021.676543

Prickett, AR, Montibus, B, Barkas, N, Amante, SM, Franco, MM, Cowley, M, Puszyk, W, Shannon, MF, Irving, MD, Madon-Simon, M, Ward, A, Schulz, R, Baldwin, HS & Oakey, RJ 2021, 'Imprinted Gene Expression and Function of the Dopa Decarboxylase Gene in the Developing Heart', Frontiers in Cell and Developmental Biology, vol. 9, 676543. https://doi.org/10.3389/fcell.2021.676543

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title = "Imprinted Gene Expression and Function of the Dopa Decarboxylase Gene in the Developing Heart",

abstract = "Dopa decarboxylase (DDC) synthesizes serotonin in the developing mouse heart where it is encoded by Ddc_exon1a, a tissue-specific paternally expressed imprinted gene. Ddc_exon1a shares an imprinting control region (ICR) with the imprinted, maternally expressed (outside of the central nervous system) Grb10 gene on mouse chromosome 11, but little else is known about the tissue-specific imprinted expression of Ddc_exon1a. Fluorescent immunostaining localizes DDC to the developing myocardium in the pre-natal mouse heart, in a region susceptible to abnormal development and implicated in congenital heart defects in human. Ddc_exon1a and Grb10 are not co-expressed in heart nor in brain where Grb10 is also paternally expressed, despite sharing an ICR, indicating they are mechanistically linked by their shared ICR but not by Grb10 gene expression. Evidence from a Ddc_exon1a gene knockout mouse model suggests that it mediates the growth of the developing myocardium and a thinning of the myocardium is observed in a small number of mutant mice examined, with changes in gene expression detected by microarray analysis. Comparative studies in the human developing heart reveal a paternal expression bias with polymorphic imprinting patterns between individual human hearts at DDC_EXON1a, a finding consistent with other imprinted genes in human.",

keywords = "dopa decarboxylase, heart, human, imprinting, knock-out, mouse",

author = "Prickett, {Adam R.} and Bertille Montibus and Nikolaos Barkas and Amante, {Samuele M.} and Franco, {Maur{\'i}cio M.} and Michael Cowley and William Puszyk and Shannon, {Matthew F.} and Irving, {Melita D.} and Marta Madon-Simon and Andrew Ward and Reiner Schulz and Baldwin, {H. Scott} and Oakey, {Rebecca J.}",

note = "Funding Information: We thank Dr. Matt Arno and the KCL genomics facility for core equipment usage. We acknowledge support from the Department of Health via the National Institute for Health Research (NIHR) Biomedical Research Centre at Guy?s and St Thomas? NHS Foundation Trust in partnership with King?s College London for access to the genomics core facility at the time directed by Dr. Alka Saxena. We thank James Cain for help with the figures, Dr. Heba Saadeh for assistance with bioinformatics analysis of the expression microarray and Dr. Sabrina B?hm for technical support. We thank the MRC-Wellcome Trust Human Developmental Biology Resource (HDBR) (http://www.hdbr.org) from the Institute of Genetic Medicine, Newcastle and Institute of Child Health, London for human fetal tissues. Funding. This work was supported by the British Heart Foundation Project Grant (PG/13/35/30236) (RO) and PhD studentship FS/08/051/25748 (to RO undertaken by AP), the Wellcome Trust Project Grant (084358/Z/07/Z) (RO), the Medical Research Council Project Grant (G1001689) (RO), the National Institutes of Health (1R01 HL118386) (HB), and EFIC facility, the National Institute of Health (S10-RR27661) (HB). ",

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AU - Prickett, Adam R.

AU - Montibus, Bertille

AU - Barkas, Nikolaos

AU - Amante, Samuele M.

AU - Franco, Maurício M.

AU - Cowley, Michael

AU - Puszyk, William

AU - Shannon, Matthew F.

AU - Irving, Melita D.

AU - Madon-Simon, Marta

AU - Ward, Andrew

AU - Schulz, Reiner

AU - Baldwin, H. Scott

AU - Oakey, Rebecca J.

N1 - Funding Information: We thank Dr. Matt Arno and the KCL genomics facility for core equipment usage. We acknowledge support from the Department of Health via the National Institute for Health Research (NIHR) Biomedical Research Centre at Guy?s and St Thomas? NHS Foundation Trust in partnership with King?s College London for access to the genomics core facility at the time directed by Dr. Alka Saxena. We thank James Cain for help with the figures, Dr. Heba Saadeh for assistance with bioinformatics analysis of the expression microarray and Dr. Sabrina B?hm for technical support. We thank the MRC-Wellcome Trust Human Developmental Biology Resource (HDBR) (http://www.hdbr.org) from the Institute of Genetic Medicine, Newcastle and Institute of Child Health, London for human fetal tissues. Funding. This work was supported by the British Heart Foundation Project Grant (PG/13/35/30236) (RO) and PhD studentship FS/08/051/25748 (to RO undertaken by AP), the Wellcome Trust Project Grant (084358/Z/07/Z) (RO), the Medical Research Council Project Grant (G1001689) (RO), the National Institutes of Health (1R01 HL118386) (HB), and EFIC facility, the National Institute of Health (S10-RR27661) (HB).

PY - 2021/6/22

Y1 - 2021/6/22

N2 - Dopa decarboxylase (DDC) synthesizes serotonin in the developing mouse heart where it is encoded by Ddc_exon1a, a tissue-specific paternally expressed imprinted gene. Ddc_exon1a shares an imprinting control region (ICR) with the imprinted, maternally expressed (outside of the central nervous system) Grb10 gene on mouse chromosome 11, but little else is known about the tissue-specific imprinted expression of Ddc_exon1a. Fluorescent immunostaining localizes DDC to the developing myocardium in the pre-natal mouse heart, in a region susceptible to abnormal development and implicated in congenital heart defects in human. Ddc_exon1a and Grb10 are not co-expressed in heart nor in brain where Grb10 is also paternally expressed, despite sharing an ICR, indicating they are mechanistically linked by their shared ICR but not by Grb10 gene expression. Evidence from a Ddc_exon1a gene knockout mouse model suggests that it mediates the growth of the developing myocardium and a thinning of the myocardium is observed in a small number of mutant mice examined, with changes in gene expression detected by microarray analysis. Comparative studies in the human developing heart reveal a paternal expression bias with polymorphic imprinting patterns between individual human hearts at DDC_EXON1a, a finding consistent with other imprinted genes in human.

AB - Dopa decarboxylase (DDC) synthesizes serotonin in the developing mouse heart where it is encoded by Ddc_exon1a, a tissue-specific paternally expressed imprinted gene. Ddc_exon1a shares an imprinting control region (ICR) with the imprinted, maternally expressed (outside of the central nervous system) Grb10 gene on mouse chromosome 11, but little else is known about the tissue-specific imprinted expression of Ddc_exon1a. Fluorescent immunostaining localizes DDC to the developing myocardium in the pre-natal mouse heart, in a region susceptible to abnormal development and implicated in congenital heart defects in human. Ddc_exon1a and Grb10 are not co-expressed in heart nor in brain where Grb10 is also paternally expressed, despite sharing an ICR, indicating they are mechanistically linked by their shared ICR but not by Grb10 gene expression. Evidence from a Ddc_exon1a gene knockout mouse model suggests that it mediates the growth of the developing myocardium and a thinning of the myocardium is observed in a small number of mutant mice examined, with changes in gene expression detected by microarray analysis. Comparative studies in the human developing heart reveal a paternal expression bias with polymorphic imprinting patterns between individual human hearts at DDC_EXON1a, a finding consistent with other imprinted genes in human.

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KW - human

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JO - Frontiers in Cell and Developmental Biology

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M1 - 676543

ER -

Imprinted Gene Expression and Function of the Dopa Decarboxylase Gene in the Developing Heart

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

Access to Document

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Imprinted genes defining a novel mammalian growth regulatory axis

MRC adipose regulation

Growth Regulation by the Grb10 and Dlk1 Signalling Protein

Cite this

Imprinted Gene Expression and Function of the Dopa Decarboxylase Gene in the Developing Heart

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Projects

Imprinted genes defining a novel mammalian growth regulatory axis

MRC adipose regulation

Growth Regulation by the Grb10 and Dlk1 Signalling Protein

Cite this