Van den Hoff group – Cardiac development

In the Netherlands every day approximately 18 (3.8%) life born children present with a congenital abnormality, of which approximately three have a congenital cardiac abnormality. Moreover, more than 100 people die daily in The Netherlands due to cardiovascular disease. The goal of research performed in my group is to understand the developmental mechanisms that are involved in normal and abnormal cardiac development and to understand the molecular response of the diseased heart, in particular after a cardiac infarction.

Contact: M.J.B. van den Hoff (

Research overview

1. Heart muscle cell formation

A 3-dimensional gel lattice in vitro explant system has been developed in which heart muscle and epicardial development can be mimicked, manipulated and analyzed using confocal laser scanning microscopy (Figure 1). In vitro and in vivo heart development is influenced by applying growth factors, cell signaling inhibitors and/or using recombinant adenoviruses. These analyses have shown that a progenitor cell population immediately upstream of the forming heart is present from which cells are recruited for the increasing number of heart muscle cells in the forming heart by Bone Morphogenetic Proteins (BMP). By Fibroblast Growth Factors (FGF) cells are recruited from this progenitor population to the non-myocardial cell population of the heart. The cooperative action of BMP and FGF retains the progenitor cells in an undifferentiated state. Genome-wide analyses have further identified Wnt signalling to be an important regulator of the size of this progenitor population, which is currently being pursued.

2. Follistatin-like 1 in the forming and adult heart

Most patients survive a first myocardial infarction (MI) as a result of efficient percutaneous coronary intervention, but will in due time develop heart failure (HF). HF develops due to the loss of cardiomyocytes and blood vessels after an MI, and their replacement with scar tissue rather than by regeneration of myocardium. Currently no therapy is available to re-initiate the cell cycle in cardiomyocytes and consequently regenerate lost cardiomyocytes. Our ultimate aim is to develop a gene therapy approach to drive gene expression within the infarct and the appropriate time window to stimulate cardiac regeneration and as a consequence delay or even prevent the development of HF.

Genome-wide analyses aiming at identifying factors that regulate cardiomyocyte formation during development and disease, have identified novel regulators of heart muscle cell and epicardium formation. These analyses identified Follistatin-like 1 (Fstl1) as a very promising candidate. Fstl1 is a secreted glycoprotein that interacts with a plethora of signaling pathways. To elucidate the biological function of Fstl1 we created a global and conditional knock-out mouse of Fstl1. The global knock-out was found to display an array of sever congenital abnormalities, among which an inability to breath. Further analysis of these death neonates revealed that their heart was more than twice as big as normal. The mechanism underlying this sever enlargement is currently being analyzed using a candidate gene approach and genome-wide analyses.

To analyze the post-natal role of Fstl1 we use conditional Fstl1 knockout mice in combination with various different Cre-driver mice, allowing the inactivation of Fstl1 in different cell populations and time points during development and adulthood .
Inactivation of Fstl1 in heart muscle cells was found to attenuate hypertrophy following pressure overload. After an experimentally induced cardiac infarction Fstl1 was found to be transiently and highly expressed in the forming infarct tissue. When Fstl1 is inactivated in the heart muscle cells the infarct increases in size, pointing to a protective role of Fstl1 in heart muscle cells. Administering Fstl1 to a cardiac infarction results in a better survival due to a smaller infarct size and better myocardial performance. On the other hand inactivating Fstl1 in the fibroblast population of the heart leads to a weakened infarct and death due to cardiac rupture within the first three days after induction of the infarct. Inactivating Fstl1 in the endocardial and endocardial-derived cells result in neonatal death. Analysis of the mice showed a severely enlarged heart and dysfunctional, very long and thick atrioventricular valves.

Interestingly, the glycosylation profile of Fstl1 changes during development and disease and might be an important regulator of the biological function of Fstl1. To assess this we have initiated studies to determine the composition and spatio-temporal changes in the various Fstl1 glycoforms during development and after an MI, as well as the expression of glycosylation-related genes. Moreover, we have created mouse lines allowing the evaluation of the role of Fstl1 in vivo during development and after the induction of an MI using conditional overexpression of glycosylated and non-glycosylated Fstl1.

As part of this project we are analyzing the transcriptional regulation of Fstl1, aiming at the identification of regulatory elements in the genomic sequences of the Fstl1 gene that drive the transient and high expression in the infarct. Identification of these regulatory elements might provide an inroad to a novel therapy in which specific therapeutic genes are transiently expressed in the forming infarct.

3. Reverse Transcriptase quantitative Polymerase Chain Reaction (RTqPCR)

Nowadays, RTqPCR is the method of choice to determine differences in gene expression. RTqPCR is considered to be straightforward and trouble free. As a consequence, most papers do not report the optimization and validation carried out to determine the specificity and sensitivity of an assay. This optimization is commonly carried out with negative and positive control samples; the loss of specific product in a dilution series of the positive sample is then considered to indicate the lower detection limit of the assay. For RTqPCR reactions with low levels of the intended product (Cq values larger than 28), it is generally recommended to check the identity of the amplified product with melting curve, size and/or sequence analysis. Unnoticed amplification of a nonspecific product (artifact), results in false positive results and possibly erroneous follow up decisions. In this research project together with Dr Jan Ruijter we aim at improving the reliability of the analysis of RTqPCR data. Dr Jan Ruijter is the developer of the LinRegPCR program, for the most up-to-date version To disseminate our knowledge, we biannually teach an advanced qPCR course, in which we cover all aspects of RTqPCR, from the isolation of the sample till the presentation of the data.

4. An atlas of 3D ultrasound images of human development

In the Western world about 3% of all live-born children have a congenital abnormality, causing 25% of all neonatal deaths. Prenatal screening using ultrasound to detect developmental abnormalities is common practice in many countries. Gross abnormalities are identified with almost 100% accuracy, whereas less than 40% of more subtle malformations are identified. This low accuracy is due to the quality of ultrasound equipment/technology and the level of operator expertise. This notion begs for improvements in technology, increasing experience, and refinements in visualization. The basis for understanding and identifying congenital abnormalities in ultrasound requires a knowledge of development. Our interactive 3D-atlas and database of human embryonic development has unveiled a wealth of novel insights. Currently, the 3D-atlas is extended towards the fetal period. However, to directly translate this information for clinical practice using 3D-ultrasound screening requires expert knowledge. Therefore, we collaborate with Samsung Medison (Korea), and Prof dr T Bourne and dr H Shah (ICL, UK) to fill this lack of knowledge. Using the Samsung Ultrasound WS80A machine with 3D-Crystal-Vue software, fetuses are scanned and further analyzed using MRI, microCT and histologically in the AMC. This workflow and our combined expert knowledge allows us to annotate structures visualized in 3D-Crystal-Vue ultrasound images and prepare an atlas of human development. Using this reference atlas health care professionals will be able to identify congenital abnormalities with high accuracy and early in pregnancy.

Figure 1. Cardiac muscle cell formation in chicken pro-epicardial collagen cultures. Red stains all nuclei of cells and green heart muscle cells. The images are scaled relative to each other (Kruithof et al. (2006) Dev Biol. 295:507-22).

Figure 2. The Cre-loxP system to target cell Lineages using genetically modified mice.

Figure 3. Expression pattern of cardiac Troponin I (cTnI) and Follistatin-like 1 (Fstl1) one week after the induction of a cardiac infarction. Note that the infarct is devoid of heart muscle cells and expresses high levels of Fstl1 (van Wijk 2012 PlosOne 7:e44692).

Figure 4. Contribution of the different cardiac cushions and ridges to the adult valves (Adapted from Lamers and Moorman (2002) Circ Res. 91:93-103).

Figure 5. Red staining identifies the cells that are derived from the endocardial-endothelial lineage (Tie2-Cre). Note that at the end of gestation the parietal leaflet is almost devoid of red endocardial-derived mesenchymal cells. Green identifies the heart muscle cells. (Wessels et al., 2012 Dev Biol 366; 111-124)

Figure 6. Proposed mechanism of Fstl1 in valve development and disease.

Figure 7. At low concentration the qPCR amplifies a artifcat (primer dimer) that can not be discriminated based on the amplification curve, but can be identified in agarose gel electrophoresis and/or melting curve analysis. (Ruiz-Villalba et al., 2017 Biomol Detect Quantif. 14: 7–18).


Maurice van den Hoff (
Jan Ruijter (
Quinn Gunst (
Jaco Hagoort (
Anita Buffing ( )
Yousif Dawood (
Marieke Buitendijk (
Harsha Shah (
Maria Cristina Festa

The development of the heart with respect to myocardial differentiation and epicardial development is studied in collaboration with the groups of Prof dr. Andy Wessels ( Medical University of South Carolina, Charleston, SC, USA), dr. José Maria Pérez-Pomares (University of Malaga, Spain) and dr José-Luis de la Pompa (Spanish National Center of Cardiovascular Research, Madrid, Spain)

The role of Follistatin like 1 is studied in collaboration with the groups of Prof dr Hans Clevers (Hubrecht Labortory, Utrecht, The Netherlands) Prof dr. Martina Schmidt (department Molecular Pharmacology, Groningen University, The Netherlands), Prof dr K Walsh (Whitaker Cardiovascular Institute, Boston University School of Medicine USA) and dr P Ruiz-Lozano (Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA).

  1. Prakash S, Mattiotti A, Sylva M, Mulder BJM, Postma AV, van den Hoff MJB. Identifying pathogenic variants in the Follistatin-like 1 gene (FSTL1) in patients with skeletal and atrioventricular valve disorders. Mol Genet Genomic Med. 2019 Apr;7(4):e00567. doi: 10.1002/mgg3.567. PMID:30722102
  2. de Bakker BS, van den Hoff MJB, Vize PD, Oostra RJ. The Pronephros; a Fresh Perspective. Integr Comp Biol. 2019 Jul 1;59(1):29-47. doi: 10.1093/icb/icz001. PMID:30649320
  3. Kretzschmar K, Post Y, Bannier-Hélaouët M, Mattiotti A, Drost J, Basak O, Li VSW, van den Born M, Gunst QD, Versteeg D, Kooijman L, van der Elst S, van Es JH, van Rooij E, van den Hoff MJB, Clevers H. Profiling proliferative cells and their progeny in damaged murine hearts. Proc Natl Acad Sci U S A. 2018 Dec 26;115(52):E12245-E12254. doi: 10.1073/pnas.1805829115. PMID: 30530645
  4. Prakash S, de Boer BA, Hagoort J, Gunst QD, Ruijter JM, van den Hoff MJB. Considerations for Measurement of Embryonic Organ Growth. Anat Rec (Hoboken). 2019 Jan;302(1):49-57. doi: 10.1002/ar.23908. PMID: 30289204
  5. Mattiotti A, Prakash S, Barnett P, van den Hoff MJB. Follistatin-like 1 in development and human diseases. Cell Mol Life Sci. 2018 Jul;75(13):2339-2354. doi: 10.1007/s00018-018-2805. PMID: 29594389
  6. Ruiz-Villalba A, van Pelt-Verkuil E, Gunst QD, Ruijter JM, van den Hoff MJ. Amplification of nonspecific products in quantitative polymerase chain reactions (qPCR). Biomol Detect Quantif. 2017 Nov 1;14:7-18. eCollection 2017 Dec.; PubMed Central PMCID: PMC5727009.
  7. de Bakker BS, Driessen S, Boukens BJD, van den Hoff MJB, Oostra RJ. Single-site neural tube closure in human embryos revisited. Clin Anat. 2017 Oct;30(7):988-999. Epub 2017 Aug 29. Review.
  8. Prakash S, Borreguero LJJ, Sylva M, Flores Ruiz L, Rezai F, Gunst QD, de la Pompa JL, Ruijter JM, van den Hoff MJB. Deletion of Fstl1 (Follistatin-Like 1) From the Endocardial/Endothelial Lineage Causes Mitral Valve Disease. Arterioscler Thromb Vasc Biol. 2017 Sep;37(9):e116-e130. Epub 2017 Jul 13.
  9. Tania NP, Maarsingh H, T Bos IS, Mattiotti A, Prakash S, Timens W, Gunst QD, Jimenez-Borreguero LJ, Schmidt M, van den Hoff MJB, Gosens R. Endothelial follistatin-like-1 regulates the postnatal development of the pulmonary vasculature by modulating BMP/Smad signaling. Pulm Circ. 2017 Mar 15;7(1):219-231. eCollection 2017 Mar.; PubMed Central PMCID: PMC5448549.
  10. Ruiz-Villalba A, Mattiotti A, Gunst QD, Cano-Ballesteros S, van den Hoff MJ, Ruijter JM. Reference genes for gene expression studies in the mouse heart. Sci Rep. 2017 Feb 2;7(1):24.; PubMed Central PMCID: PMC5428317.
  11. Tanaka K, Valero-Muñoz M, Wilson RM, Essick EE, Fowler CT, Nakamura K, van den Hoff M, Ouchi N, Sam F. Follistatin like 1 Regulates Hypertrophy in Heart Failure with Preserved Ejection Fraction. JACC Basic Transl Sci. 2016 Jun;1(4):207-221. Epub 2016 Jun 27.; PubMed Central PMCID: PMC4944656.
  12. Hibender S, Franken R, van Roomen C, Ter Braake A, van der Made I, Schermer EE, Gunst Q, van den Hoff MJ, Lutgens E, Pinto YM, Groenink M, Zwinderman AH, Mulder BJ, de Vries CJ, de Waard V. Resveratrol Inhibits Aortic Root Dilatation in the Fbn1C1039G/+ Marfan Mouse Model. Arterioscler Thromb Vasc Biol. 2016 Aug;36(8):1618-26. Epub 2016 Jun 9. Erratum in: Arterioscler Thromb Vasc Biol. 2016 Sep;36(9):e81.; PubMed Central PMCID: PMC4961273.
  13. Maruyama S, Nakamura K, Papanicolaou KN, Sano S, Shimizu I, Asaumi Y, van den Hoff MJ, Ouchi N, Recchia FA, Walsh K. Follistatin-like 1 promotes cardiac fibroblast activation and protects the heart from rupture. EMBO Mol Med. 2016 Aug 1;8(8):949-66. Print 2016 Aug.; PubMed Central PMCID: PMC4967946.
  14. Ruijter JM, Ruiz Villalba A, Hellemans J, Untergasser A, van den Hoff MJ. Removal of between-run variation in a multi-plate qPCR experiment. Biomol Detect Quantif. 2015 Jul 30;5:10-4. eCollection 2015 Sep.; PubMed Central PMCID: PMC4822202.
  15. Pérez-Pomares JM, de la Pompa JL, Franco D, Henderson D, Ho SY, Houyel L, Kelly RG, Sedmera D, Sheppard M, Sperling S, Thiene G, van den Hoff M, Basso C. Congenital coronary artery anomalies: a bridge from embryology to anatomy and pathophysiology–a position statement of the development, anatomy, and pathology ESC Working Group. Cardiovasc Res. 2016 Feb 1;109(2):204-16. Epub 2016 Jan 11. Review.
  16. Ruiz-Villalba A, Hoppler S, van den Hoff MJ. Wnt signaling in the heart fields: Variations on a common theme. Dev Dyn. 2016 Mar;245(3):294-306. Epub 2016 Jan 6. Review.
  17. Wei K, Serpooshan V, Hurtado C, Diez-Cuñado M, Zhao M, Maruyama S, Zhu W, Fajardo G, Noseda M, Nakamura K, Tian X, Liu Q, Wang A, Matsuura Y, Bushway P, Cai W, Savchenko A, Mahmoudi M, Schneider MD, van den Hoff MJ, Butte MJ, Yang PC, Walsh K, Zhou B, Bernstein D, Mercola M, Ruiz-Lozano P. Epicardial FSTL1 reconstitution regenerates the adult mammalian heart. Nature. 2015 Sep 24;525(7570):479-85. Epub 2015 Sep 16.; PubMed Central PMCID: PMC4762253.
  18. Briggs LE, Burns TA, Lockhart MM, Phelps AL, Van den Hoff MJ, Wessels A. Wnt/β-catenin and sonic hedgehog pathways interact in the regulation of the development of the dorsal mesenchymal protrusion. Dev Dyn. 2016 Feb;245(2):103-13. Epub 2015 Dec 29.; PubMed Central PMCID: PMC4978225.
  19. Lockhart MM, Boukens BJ, Phelps AL, Brown CL, Toomer KA, Burns TA, Mukherjee RD, Norris RA, Trusk TC, van den Hoff MJ, Wessels A. Alk3 mediated Bmp signaling controls the contribution of epicardially derived cells to the tissues of the atrioventricular junction. Dev Biol. 2014 Dec 1;396(1):8-18. Epub 2014 Oct 6.; PubMed Central PMCID: PMC4252836.
  20. Ruijter JM, Lorenz P, Tuomi JM, Hecker M, van den Hoff MJ. Fluorescent-increase kinetics of different fluorescent reporters used for qPCR depend on monitoring chemistry, targeted sequence, type of DNA input and PCR efficiency. Mikrochim Acta. 2014;181(13-14):1689-1696. Epub 2014 Jan 14.; PubMed Central PMCID: PMC4167442.
  21. Hayakawa S, Ohashi K, Shibata R, Kataoka Y, Miyabe M, Enomoto T, Joki Y, Shimizu Y, Kambara T, Uemura Y, Yuasa D, Ogawa H, Matsuo K, Hiramatsu-Ito M, van den Hoff MJ, Walsh K, Murohara T, Ouchi N. Cardiac myocyte-derived follistatin-like 1 prevents renal injury in a subtotal nephrectomy model. J Am Soc Nephrol. 2015 Mar;26(3):636-46. Epub 2014 Jul 28.; PubMed Central PMCID: PMC4341480.
  22. Lockhart MM, Phelps AL, van den Hoff MJ, Wessels A. The Epicardium and the Development of the Atrioventricular Junction in the Murine Heart. J Dev Biol. 2014 Mar 1;2(1):1-17.; PubMed Central PMCID: PMC4051323.
  23. Miyabe M, Ohashi K, Shibata R, Uemura Y, Ogura Y, Yuasa D, Kambara T, Kataoka Y, Yamamoto T, Matsuo K, Joki Y, Enomoto T, Hayakawa S, Hiramatsu-Ito M, Ito M, Van Den Hoff MJ, Walsh K, Murohara T, Ouchi N. Muscle-derived follistatin-like 1 functions to reduce neointimal formation after vascular injury. Cardiovasc Res. 2014 Jul 1;103(1):111-20. Epub 2014 Apr 17.; PubMed Central PMCID: PMC4834864.
  24. Velecela V, Lettice LA, Chau YY, Slight J, Berry RL, Thornburn A, Gunst QD, van den Hoff M, Reina M, Martínez FO, Hastie ND, Martínez-Estrada OM. WT1 regulates the expression of inhibitory chemokines during heart development. Hum Mol Genet. 2013 Dec 20;22(25):5083-95. Epub 2013 Jul 29.
  25. Sylva M, Moorman AF, van den Hoff MJ. Follistatin-like 1 in vertebrate development. Birth Defects Res C Embryo Today. 2013 Mar;99(1):61-9. Review.
  26. Sylva M, van den Hoff MJ, Moorman AF. Development of the human heart. Am J Med Genet A. 2014 Jun;164A(6):1347-71. Epub 2013 Apr 30. Review.
  27. Briggs LE, Phelps AL, Brown E, Kakarla J, Anderson RH, van den Hoff MJ, Wessels A. Expression of the BMP receptor Alk3 in the second heart field is essential for development of the dorsal mesenchymal protrusion and atrioventricular septation. Circ Res. 2013 May 24;112(11):1420-32. Epub 2013 Apr 12.; PubMed Central PMCID: PMC3822333.
  28. de Boer BA, van den Berg G, Soufan AT, de Boer PA, Hagoort J, van den Hoff MJ, Moorman AF, Ruijter JM. Measurement and 3D-visualization of cell-cycle length using double labelling with two thymidine analogues applied in early heart development. PLoS One. 2012;7(10):e47719. Epub 2012 Oct 16.; PubMed Central PMCID: PMC3473012.
  29. van Wijk B, Gunst QD, Moorman AF, van den Hoff MJ. Cardiac regeneration from activated epicardium. PLoS One. 2012;7(9):e44692. Epub 2012 Sep 20.; PubMed Central PMCID: PMC3447884.
  30. Jensen B, Boukens BJ, Postma AV, Gunst QD, van den Hoff MJ, Moorman AF, Wang T, Christoffels VM. Identifying the evolutionary building blocks of the cardiac conduction system. PLoS One. 2012;7(9):e44231. Epub 2012 Sep 11.; PubMed Central PMCID: PMC3439475.
  31. van Oppenraaij RH, Koning AH, van den Hoff MJ, van der Spek PJ, Steegers EA, Exalto N. The effect of smoking on early chorionic villous vascularisation. Placenta. 2012 Aug;33(8):645-51. Epub 2012 Jun 12.
  32. Wessels A, van den Hoff MJ, Adamo RF, Phelps AL, Lockhart MM, Sauls K, Briggs LE, Norris RA, van Wijk B, Perez-Pomares JM, Dettman RW, Burch JB. Epicardially derived fibroblasts preferentially contribute to the parietal leaflets of the atrioventricular valves in the murine heart. Dev Biol. 2012 Jun 15;366(2):111-24. Epub 2012 Apr 24.; PubMed Central PMCID: PMC3358438.
  33. Shimano M, Ouchi N, Nakamura K, van Wijk B, Ohashi K, Asaumi Y, Higuchi A, Pimentel DR, Sam F, Murohara T, van den Hoff MJ, Walsh K. Cardiac myocyte follistatin-like 1 functions to attenuate hypertrophy following pressure overload. Proc Natl Acad Sci U S A. 2011 Oct 25;108(43):E899-906. Epub 2011 Oct 10.; PubMed Central PMCID: PMC3203781.
  34. Sylva M, Li VS, Buffing AA, van Es JH, van den Born M, van der Velden S, Gunst Q, Koolstra JH, Moorman AF, Clevers H, van den Hoff MJ. The BMP antagonist follistatin-like 1 is required for skeletal and lung organogenesis. PLoS One. 2011;6(8):e22616. Epub 2011 Aug 3.; PubMed Central PMCID: PMC3149603.
  35. Barnett P, van den Hoff MJ. Cardiac regeneration: different cells same goal. Med Biol Eng Comput. 2011 Jul;49(7):723-32. Epub 2011 Apr 16. Review.; PubMed Central PMCID: PMC3121945.
  36. Buermans HP, van Wijk B, Hulsker MA, Smit NC, den Dunnen JT, van Ommen GB, Moorman AF, van den Hoff MJ, ‘t Hoen PA. Comprehensive gene-expression survey identifies wif1 as a modulator of cardiomyocyte differentiation. PLoS One. 2010 Dec 13;5(12):e15504.; PubMed Central PMCID: PMC3001492.
  37. de Boer BA, Soufan AT, Hagoort J, Mohun TJ, van den Hoff MJ, Hasman A, Voorbraak FP, Moorman AF, Ruijter JM. The interactive presentation of 3D information obtained from reconstructed datasets and 3D placement of single histological sections with the 3D portable document format. Development. 2011 Jan;138(1):159-67.; PubMed Central PMCID: PMC2998169.
  38. Chakrabarti SK, Wen Y, Dobrian AD, Cole BK, Ma Q, Pei H, Williams MD, Bevard MH, Vandenhoff GE, Keller SR, Gu J, Nadler JL. Evidence for activation of inflammatory lipoxygenase pathways in visceral adipose tissue of obese Zucker rats. Am J Physiol Endocrinol Metab. 2011 Jan;300(1):E175-87. Epub 2010 Oct 26.; PubMed Central PMCID: PMC3023204.
  39. van Wijk B, van den Hoff M. Epicardium and myocardium originate from a common cardiogenic precursor pool. Trends Cardiovasc Med. 2010 Jan;20(1):1-7. Review.
  40. Norden J, Grieskamp T, Lausch E, van Wijk B, van den Hoff MJ, Englert C, Petry M, Mommersteeg MT, Christoffels VM, Niederreither K, Kispert A. Wt1 and retinoic acid signaling in the subcoelomic mesenchyme control the development of the pleuropericardial membranes and the sinus horns. Circ Res. 2010 Apr 16;106(7):1212-20. Epub 2010 Feb 25.; PubMed Central PMCID: PMC2862253.
  41. Pilichou K, Remme CA, Basso C, Campian ME, Rizzo S, Barnett P, Scicluna BP, Bauce B, van den Hoff MJ, de Bakker JM, Tan HL, Valente M, Nava A, Wilde AA, Moorman AF, Thiene G, Bezzina CR. Myocyte necrosis underlies progressive myocardial dystrophy in mouse dsg2-related arrhythmogenic right ventricular cardiomyopathy. J Exp Med. 2009 Aug 3;206(8):1787-802. Epub 2009 Jul 27.; PubMed Central PMCID: PMC2722163.
  42. van Wijk B, van den Berg G, Abu-Issa R, Barnett P, van der Velden S, Schmidt M, Ruijter JM, Kirby ML, Moorman AF, van den Hoff MJ. Epicardium and myocardium separate from a common precursor pool by crosstalk between bone morphogenetic protein- and fibroblast growth factor-signaling pathways. Circ Res. 2009 Aug 28;105(5):431-41. Epub 2009 Jul 23.; PubMed Central PMCID: PMC2861358.
  43. Campian ME, Verberne HJ, Hardziyenka M, de Bruin K, Selwaness M, van den Hoff MJ, Ruijter JM, van Eck-Smit BL, de Bakker JM, Tan HL. Serial noninvasive assessment of apoptosis during right ventricular disease progression in rats. J Nucl Med. 2009 Aug;50(8):1371-7. Epub 2009 Jul 17.
  44. Remme CA, Verkerk AO, Hoogaars WM, Aanhaanen WT, Scicluna BP, Annink C, van den Hoff MJ, Wilde AA, van Veen TA, Veldkamp MW, de Bakker JM, Christoffels VM, Bezzina CR. The cardiac sodium channel displays differential distribution in the conduction system and transmural heterogeneity in the murine ventricular myocardium. Basic Res Cardiol. 2009 Sep;104(5):511-22. Epub 2009 Mar 3.; PubMed Central PMCID: PMC2722719.
  45. Ruijter JM, Ramakers C, Hoogaars WM, Karlen Y, Bakker O, van den Hoff MJ, Moorman AF. Amplification efficiency: linking baseline and bias in the analysis of quantitative PCR data. Nucleic Acids Res. 2009 Apr;37(6):e45. Epub 2009 Feb 22.; PubMed Central PMCID: PMC2665230.
  46. van Oppenraaij RH, Koning AH, Lisman BA, Boer K, van den Hoff MJ, van der Spek PJ, Steegers EA, Exalto N. Vasculogenesis and angiogenesis in the first trimester human placenta: an innovative 3D study using an immersive Virtual Reality system. Placenta. 2009 Mar;30(3):220-2. Epub 2009 Jan 31.
  47. van den Berg G, Abu-Issa R, de Boer BA, Hutson MR, de Boer PA, Soufan AT, Ruijter JM, Kirby ML, van den Hoff MJ, Moorman AF. A caudal proliferating growth center contributes to both poles of the forming heart tube. Circ Res. 2009 Jan 30;104(2):179-88. Epub 2008 Dec 4.; PubMed Central PMCID: PMC2683147.
  48. Moorman AF, Christoffels VM, Anderson RH, van den Hoff MJ. The heart-forming fields: one or multiple? Philos Trans R Soc Lond B Biol Sci. 2007 Aug 29;362(1484):1257-65. Review.; PubMed Central PMCID: PMC2440394.
  49. van den Berg G, Somi S, Buffing AA, Moorman AF, van den Hoff MJ. Patterns of expression of the Follistatin and Follistatin-like1 genes during chicken heart development: a potential role in valvulogenesis and late heart muscle cell formation. Anat Rec (Hoboken). 2007 Jul;290(7):783-7.
  50. Lisman BA, van den Hoff MJ, Boer K, Bleker OP, van Groningen K, Exalto N. The architecture of first trimester chorionic villous vascularization: a confocal laser scanning microscopical study. Hum Reprod. 2007 Aug;22(8):2254-60. Epub 2007 Jun 1.
  51. Barendrecht MM, Mulders AC, van der Poel H, van den Hoff MJ, Schmidt M, Michel MC. Role of transforming growth factor beta in rat bladder smooth muscle cell proliferation. J Pharmacol Exp Ther. 2007 Jul;322(1):117-22. Epub 2007 Apr 13.
  52. Soufan AT, van den Berg G, Moerland PD, Massink MM, van den Hoff MJ, Moorman AF, Ruijter JM. Three-dimensional measurement and visualization of morphogenesis applied to cardiac embryology. J Microsc. 2007 Mar;225(Pt 3):269-74.
  53. Rana MS, Horsten NC, Tesink-Taekema S, Lamers WH, Moorman AF, van den Hoff MJ. Trabeculated right ventricular free wall in the chicken heart forms by ventricularization of the myocardium initially forming the outflow tract. Circ Res. 2007 Apr 13;100(7):1000-7. Epub 2007 Mar 8.
  54. van Wijk B, Moorman AF, van den Hoff MJ. Role of bone morphogenetic proteins in cardiac differentiation. Cardiovasc Res. 2007 May 1;74(2):244-55. Epub 2006 Nov 21. Review.
  55. Soufan AT, van den Berg G, Ruijter JM, de Boer PA, van den Hoff MJ, Moorman AF. Regionalized sequence of myocardial cell growth and proliferation characterizes early chamber formation. Circ Res. 2006 Sep 1;99(5):545-52. Epub 2006 Aug 3.
  56. Mommersteeg MT, Soufan AT, de Lange FJ, van den Hoff MJ, Anderson RH, Christoffels VM, Moorman AF. Two distinct pools of mesenchyme contribute to the development of the atrial septum. Circ Res. 2006 Aug 18;99(4):351-3. Epub 2006 Jul 27.
  57. Kruithof BP, van Wijk B, Somi S, Kruithof-de Julio M, Pérez Pomares JM, Weesie F, Wessels A, Moorman AF, van den Hoff MJ. BMP and FGF regulate the differentiation of multipotential pericardial mesoderm into the myocardial or epicardial lineage. Dev Biol. 2006 Jul 15;295(2):507-22. Epub 2006 Apr 3. PubMed PMID: 16753139.
  58. van den Hoff MJ, Postma AV, Michel MC. Candidate genes for the hereditary component of cardiac hypertrophy. J Hypertens. 2006 Feb;24(2):273-7.
  59. Moralez I, Phelps A, Riley B, Raines M, Wirrig E, Snarr B, Jin JP, Van Den Hoff M, Hoffman S, Wessels A. Muscularizing tissues in the endocardial cushions of the avian heart are characterized by the expression of h1-calponin. Dev Dyn. 2006 Jun;235(6):1648-58.
  60. Somi S, Klein AT, Houweling AC, Ruijter JM, Buffing AA, Moorman AF, van den Hoff MJ. Atrial and ventricular myosin heavy-chain expression in the developing chicken heart: strengths and limitations of non-radioactive in situ hybridization. J Histochem Cytochem. 2006 Jun;54(6):649-64. Epub 2006 Feb 6.
  61. Schimmel K, Bennink R, de Bruin K, Leen R, Sand K, van den Hoff M, van Kuilenburg A, Vanderheyden JL, Steinmetz N, Pfaffendorf M, Verschuur A, Guchelaar HJ. Absence of cardiotoxicity of the experimental cytotoxic drug cyclopentenyl cytosine (CPEC) in rats. Arch Toxicol. 2005 May;79(5):268-76. Epub 2005 Feb 2.
  62. van den Hoff MJ, Moorman AF. Wnt, a driver of myocardialization? Circ Res. 2005 Feb 18;96(3):274-6. Review.
  63. Soufan AT, van den Hoff MJ, Ruijter JM, de Boer PA, Hagoort J, Webb S, Anderson RH, Moorman AF. Reconstruction of the patterns of gene expression in the developing mouse heart reveals an architectural arrangement that facilitates the understanding of atrial malformations and arrhythmias. Circ Res. 2004 Dec 10;95(12):1207-15. Epub 2004 Nov 18.
  64. van den Hoff MJ, Deprez RH, Ruijter JM, de Boer PA, Tesink-Taekema S, Buffing AA, Lamers WH, Moorman AF. Increased cardiac workload by closure of the ductus arteriosus leads to hypertrophy and apoptosis rather than to hyperplasia in the late fetal period. Naunyn Schmiedebergs Arch Pharmacol. 2004 Sep;370(3):193-202. Epub 2004 Aug 31.
  65. de Lange FJ, Moorman AF, Anderson RH, Männer J, Soufan AT, de Gier-de Vries C, Schneider MD, Webb S, van den Hoff MJ, Christoffels VM. Lineage and morphogenetic analysis of the cardiac valves. Circ Res. 2004 Sep 17;95(6):645-54. Epub 2004 Aug 5.
  66. Somi S, Buffing AA, Moorman AF, Van Den Hoff MJ. Dynamic patterns of expression of BMP isoforms 2, 4, 5, 6, and 7 during chicken heart development. Anat Rec A Discov Mol Cell Evol Biol. 2004 Jul;279(1):636-51.
  67. Somi S, Buffing AA, Moorman AF, Van Den Hoff MJ. Expression of bone morphogenetic protein-10 mRNA during chicken heart development. Anat Rec A Discov Mol Cell Evol Biol. 2004 Jul;279(1):579-82.
  68. Bennink RJ, van den Hoff MJ, van Hemert FJ, de Bruin KM, Spijkerboer AL, Vanderheyden JL, Steinmetz N, van Eck-Smit BL. Annexin V imaging of acute doxorubicin cardiotoxicity (apoptosis) in rats. J Nucl Med. 2004 May;45(5):842-8.
  69. van den Hoff MJ, Kruithof BP, Moorman AF. Making more heart muscle. Bioessays. 2004 Mar;26(3):248-61. Review.
  70. Lombardi MP, van den Hoff MJ, Ruijter JM, Luijerink M, Buffing AA, Markman MW, Moorman AF, Lekanne Deprez RH. Expression analysis of subtractively enriched libraries (EASEL): a widely applicable approach to the identification of differentially expressed genes. J Biochem Biophys Methods. 2003 Jul 31;57(1):17-33.
  71. Somi S, Houweling AC, Buffing AA, Moorman AF, Van Den Hoff MJ. Expression of cVg1 mRNA during chicken embryonic development. Anat Rec A Discov Mol Cell Evol Biol. 2003 Jul;273(1):603-8.
  72. Soufan AT, Ruijter JM, van den Hoff MJ, de Boer PA, Hagoort J, Moorman AF. Three-dimensional reconstruction of gene expression patterns during cardiac development. Physiol Genomics. 2003 May 13;13(3):187-95. Epub 2003 May 13. Review.
  73. Kruithof BP, van den Hoff MJ, Wessels A, Moorman AF. Cardiac muscle cell formation after development of the linear heart tube. Dev Dyn. 2003 May;227(1):1-13.
  74. Kruithof BP, Van Den Hoff MJ, Tesink-Taekema S, Moorman AF. Recruitment of intra- and extracardiac cells into the myocardial lineage during mouse development. Anat Rec A Discov Mol Cell Evol Biol. 2003 Apr;271(2):303-14.
  75. Houweling AC, Somi S, Van Den Hoff MJ, Moorman AF, Christoffels VM. Developmental pattern of ANF gene expression reveals a strict localization of cardiac chamber formation in chicken. Anat Rec. 2002 Feb 1;266(2):93-102. PubMed PMID: 11788942.
  76. van den Hoff MJ, Kruithof BP, Moorman AF, Markwald RR, Wessels A. Formation of myocardium after the initial development of the linear heart tube. Dev Biol. 2001 Dec 1;240(1):61-76.
  77. van den Eijnde SM, van den Hoff MJ, Reutelingsperger CP, van Heerde WL, Henfling ME, Vermeij-Keers C, Schutte B, Borgers M, Ramaekers FC. Transient expression of phosphatidylserine at cell-cell contact areas is required for myotube formation. J Cell Sci. 2001 Oct;114(Pt 20):3631-42.
  78. Remme CA, Lombardi MP, van den Hoff MJ, Lekanne dit Deprez RH. CDNA arrays: the ups and downs. Cardiovasc Drugs Ther. 2001 Mar;15(2):99-101.
  79. Spijkers JA, van den Hoff MJ, Hakvoort TB, Vermeulen JL, Tesink-Taekema S, Lamers WH. Foetal rise in hepatic enzymes follows decline in c-met and hepatocyte growth factor expression. J Hepatol. 2001 May;34(5):699-710.
  80. Demolombe S, Lande G, Charpentier F, van Roon MA, van den Hoff MJ, Toumaniantz G, Baro I, Guihard G, Le Berre N, Corbier A, de Bakker J, Opthof T, Wilde A, Moorman AF, Escande D. Transgenic mice overexpressing human KvLQT1 dominant-negative isoform. Part I: Phenotypic characterisation. Cardiovasc Res. 2001 May;50(2):314-27.
  81. van den Hoff MJ, Moorman AF. Cardiac neural crest: the holy grail of cardiac abnormalities? Cardiovasc Res. 2000 Aug;47(2):212-6. Review.
  82. Moorman AF, Schumacher CA, de Boer PA, Hagoort J, Bezstarosti K, van den Hoff MJ, Wagenaar GT, Lamers JM, Wuytack F, Christoffels VM, Fiolet JW. Presence of functional sarcoplasmic reticulum in the developing heart and its confinement to chamber myocardium. Dev Biol. 2000 Jul 15;223(2):279-90.
  83. van den Hoff MJ, van den Eijnde SM, Virágh S, Moorman AF. Programmed cell death in the developing heart. Cardiovasc Res. 2000 Feb;45(3):603-20. Review.
  84. van den Hoff MJ, Moorman AF. Measure is treasure. Cardiovasc Res. 1999 Aug 1;43(2):288-90.
  85. van den Hoff MJ, Moorman AF, Ruijter JM, Lamers WH, Bennington RW, Markwald RR, Wessels A. Myocardialization of the cardiac outflow tract. Dev Biol. 1999 Aug 15;212(2):477-90.
  86. Mohammad-Panah R, Demolombe S, Neyroud N, Guicheney P, Kyndt F, van den Hoff M, Baró I, Escande D. Mutations in a dominant-negative isoform correlate with phenotype in inherited cardiac arrhythmias. Am J Hum Genet. 1999 Apr;64(4):1015-23.; PubMed Central PMCID: PMC1377825.
  87. Korver W, Schilham MW, Moerer P, van den Hoff MJ, Dam K, Lamers WH, Medema RH, Clevers H. Uncoupling of S phase and mitosis in cardiomyocytes and hepatocytes lacking the winged-helix transcription factor Trident. Curr Biol. 1998 Dec 3;8(24):1327-30.
  88. LekanneDeprez RH, van den Hoff MJ, de Boer PA, Ruijter PM, Maas AA, Chamuleau RA, Lamers WH, Moorman AF. Changing patterns of gene expression in the pulmonary trunk-banded rat heart. J Mol Cell Cardiol. 1998 Sep;30(9):1877-88.
  89. Ya J, van den Hoff MJ, de Boer PA, Tesink-Taekema S, Franco D, Moorman AF, Lamers WH. Normal development of the outflow tract in the rat. Circ Res. 1998 Mar 9;82(4):464-72.
  90. Jonker A, de Boer PA, van den Hoff MJ, Lamers WH, Moorman AF. Towards quantitative in situ hybridization. J Histochem Cytochem. 1997 Mar;45(3):413-23.
  91. van den Hoff MJ, Deprez RH, Monteiro M, de Boer PA, Charles R, Moorman AF. Developmental changes in rat cardiac DNA, RNA and protein tissue base: implications for the interpretation of changes in gene expression. J Mol Cell Cardiol. 1997 Feb;29(2):629-39.
  92. Drewnowska K, Labruyere WT, van den Hoff MJ, Lamers WH, Schoolwerth AC. Stimulation of phosphoenolpyruvate carboxykinase gene expression in cultured LLC-PK1-F+ cells. Contrib Nephrol. 1997;121:25-30.
  93. Christoffels VM, van den Hoff MJ, Lamers MC, van Roon MA, de Boer PA, Moorman AF, Lamers WH. The upstream regulatory region of the carbamoyl-phosphate synthetase I gene controls its tissue-specific, developmental, and hormonal regulation in vivo. J Biol Chem. 1996 Dec 6;271(49):31243-50.
  94. van den Hoff MJ, Jonker A, Beintema JJ, Lamers WH. Evolutionary relationships of the carbamoylphosphate synthetase genes. J Mol Evol. 1995 Dec;41(6):813-32.
  95. Christoffels VM, van den Hoff MJ, Moorman AF, Lamers WH. The far-upstream enhancer of the carbamoyl-phosphate synthetase I gene is responsible for the tissue specificity and hormone inducibility of its expression. J Biol Chem. 1995 Oct 20;270(42):24932-40.
  96. van den Hoff MJ, van de Zande LP, Dingemanse MA, Das AT, Labruyère W, Moorman AF, Charles R, Lamers WH. Isolation and characterization of the rat gene for carbamoylphosphate synthetase I. Eur J Biochem. 1995 Mar 1;228(2):351-61. PubMed PMID: 7705349.
  97. van den Hoff MJ, Christoffels VM, Labruyère WT, Moorman AF, Lamers WH. Electrotransfection with “intracellular” buffer. Methods Mol Biol. 1995;48:185-97.
  98. Van den Hoff MJ, Vermeulen JL, De Boer PA, Lamers WH, Moorman AF. Developmental changes in the expression of the liver-enriched transcription factors LF-B1, C/EBP, DBP and LAP/LIP in relation to the expression of albumin, alpha-fetoprotein, carbamoylphosphate synthase and lactase mRNA. Histochem J. 1994 Jan;26(1):20-31.
  99. van den Hoff MJ, Labruyère WT, Moorman AF, Lamers WH. Mammalian gene expression is improved by use of a longer SV40 early polyadenylation cassette. Nucleic Acids Res. 1993 Oct 25;21(21):4987-8.; PubMed Central PMCID: PMC311420.
  100. van den Hoff MJ, Moorman AF, Lamers WH. Electroporation in ‘intracellular’ buffer increases cell survival. Nucleic Acids Res. 1992 Jun 11;20(11):2902.; PubMed Central PMCID: PMC336954.
  101. Van den Hoff MJ, Geerts WJ, Das AT, Moorman AF, Lamers WH. cDNA sequence of the long mRNA for human glutamine synthase. Biochim Biophys Acta. 1991 Oct 8;1090(2):249-51.
  102. Moorman AF, van den Hoff MJ, de Boer PA, Charles R, Lamers WH. The dynamics of the expression of C/EBP mRNA in the adult rat liver lobulus qualifies it as a pericentral mRNA. FEBS Lett. 1991 Aug 19;288(1-2):133-7.
  103. van den Hoff MJ, Labruyère WT, Moorman AF, Lamers WH. The osmolarity of the electroporation medium affects the transient expression of genes. Nucleic Acids Res. 1990 Nov 11;18(21):6464.; PubMed Central PMCID: PMC332585.