Homeobox Genes and Homeodomain Proteins: New Insights into Cardiac Development, Degeneration and Regeneration

  • Rokas Miksiunas
  • Ali Mobasheri
  • Daiva BironaiteEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1212)


Cardiovascular diseases are the most common cause of human death in the developing world. Extensive evidence indicates that various toxic environmental factors and unhealthy lifestyle choices contribute to the risk, incidence and severity of cardiovascular diseases. Alterations in the genetic level of myocardium affects normal heart development and initiates pathological processes leading to various types of cardiac diseases. Homeobox genes are a large and highly specialized family of closely related genes that direct the formation of body structure, including cardiac development. Homeobox genes encode homeodomain proteins that function as transcription factors with characteristic structures that allow them to bind to DNA, regulate gene expression and subsequently control the proper physiological function of cells, tissues and organs. Mutations in homeobox genes are rare and usually lethal with evident alterations in cardiac function at or soon after the birth. Our understanding of homeobox gene family expression and function has expanded significantly during the recent years. However, the involvement of homeobox genes in the development of human and animal cardiac tissue requires further investigation. The phenotype of human congenital heart defects unveils only some aspects of human heart development. Therefore, mouse models are often used to gain a better understanding of human heart function, pathology and regeneration. In this review, we have focused on the role of homeobox genes in the development and pathology of human heart as potential tools for the future development of targeted regenerative strategies for various heart malfunctions.


Cardiac development Cardiac regeneration Heart disease Homeobox genes 



atrial myosin heavy chain-1




bone morphogenetic protein


cadherin 2


cyclin-dependent kinases


Cbp/P300 interacting transactivator with Glu/Asp Rich Carboxy-Terminal Domain 2


central nerve system


embryonic stem cells


fibroblast growth factor


first heart field


fetal liver kinase 1


gap junction protein alpha 5




histone H3 methylation on the amino (N) terminal tail


hyperpolarization-activated cyclic nucleotide-gated channel 4 gene


homeobox transcription factor Hox-like


Iroquois family of homeobox genes


LIM-homeodomain transcription factor islet 1/insulin gene enhancer protein ISL-1


JmjC domain-containing protein 3


myocyte-specific enhancer factor 2C


mesoderm posterior BHLH transcription factor 1


mesenchymal stem cells






homeobox protein NK-2 homolog E


nodal growth differentiation factor


natriuretic peptide A


outflow tract


poly(rC)-binding protein 2


paired like homeodomain 2


paired-like homeodomain transcription factor 2




retinoic acid


sinoatrial node


second heart field


short stature homeobox 2


main signal transducers for receptors of the transforming growth factor beta (TGF-β) superfamily;


three-amino-acid loop extension


T-box transcription factor 5


transcription factors


transforming growth factor beta;


ventricular conduction system


zinc finger E-box binding homeobox 2


zinc finger


zebrafish iroquois homeobox genes


tight junction protein 3



The study is funded by the Lithuanian Research council, project No. S-MIP-17-13.

Ethics Approval and Consent to Participate

Not applicable.

Consent for Publication

All authors agree to the publication of this manuscript.

Availability of Data and Material

Not applicable.

Competing Interests

The authors declare that they have no competing interests.

Authors’ Contributions

RM wrote the manuscript draft. DB revised the manuscript. AM read, corrected and approved the final manuscript.


The study is funded by the Lithuanian Research council, project No. S-MIP-17-13.


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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Rokas Miksiunas
    • 1
  • Ali Mobasheri
    • 1
  • Daiva Bironaite
    • 1
    Email author
  1. 1.Department of Regenerative MedicineState Research Institute Centre for Innovative MedicineVilniusLithuania

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