Tinman gene

tinman, or tin is an Nk2-homeobox containing transcription factor first isolated in Drosophila files. The human homolog is the Nkx2-5 gene. tinman is expressed in the precardiac mesoderm and is responsible for the differentiation, proliferation, and specification of cardiac progenitor cells.[1][2]

Function and homologues

Homeobox genes are a group of transcription factors characterized by a homeodomain that initiates gene expression which regulates cell differentiation and development when it binds to a target promoter.[3] tinman was first isolated in Drosophila and many vertebrate homologs have been discovered since and are considered part of a multigene family in vertebrates. The human homolog is Nkx2-5.

tinman is dependent upon the JAK-STAT signalling of the precardiac mesoderm to differentiate into a more confined growth pattern for development of visceral mesoderm and the heart.[4] It contributes to the looping of the heart during fetal cardiac development, but has also been found to contribute to the regulation of the heart's electrical system postnatally.[4]

Expression

tinman is expressed very early in Drosophila during the development of the embryonic mesoderm and is required for formation of the visceral and cardiac mesoderm. It is expressed transiently in the visceral mesoderm but continues to be expressed in the cardiac mesoderm. The two major cell types of the Drosophila heart, cardial and pericardial cells, express tinman.[1]

Clinical Significance

In both Drosophila and vertebrates, the temporal and spatial expression of tinman is critical in determining cell lineage and patterning of the heart. In mutant or knockout organisms, the loss of tinman results in the lack of heart formation. In humans, mutations of Nkx2.5 result in some of the most common congenital heart defects. These include atrial and ventricular septal defects and tetralogy of Fallot.[5] Abnormal placental expression of Nkx2.5 has been associated with some cases of severe, early onset preeclampsia.[6]

References

  1. 1 2 Evans, Sylvia; Yan, Wei; Murillo, M. Patricia; Ponce, Jeanette; Papalopulu, Nancy (November 1, 1995). "tinman, a Drosophila homeobox gene required for heart and visceral mesoderm specification, may be represented by a family of genes in vertebrates: XNkx-2.3, a second vertebrate homolog of tin man" (PDF). Development (121): 3889–3899. Retrieved 15 April 2014.
  2. ↑ Cokkinos, Dennis V. (2014). Introduction to Translational Cardiovascular Research. Springer. p. 19. ISBN 9783319087986.
  3. ↑ Fu, Yuchang; Pilar Ruiz-Lozano; Sylvia M. Evans (June 1997). "A rat homeobox gene, rNKx-2.5, is a homologue of the tinman gene in Drosophila and is mainly expressed during heart development" (PDF). Developmental Genes and Evolution (207): 352–358. Retrieved 15 April 2014.
  4. ↑ Bodmer, R. (1993-07-01). "The gene tinman is required for specification of the heart and visceral muscles in Drosophila". Development. 118 (3): 719–729. ISSN 0950-1991.
  5. ↑ "Recent Advances in Cardiovascular Development". Circulation Research. 113 (11): e102–e105. 7 November 2013. doi:10.1161/CIRCRESAHA.113.302820.
  6. ↑ Rivers, Elena R. et. al. (2014). "Placental Nkx2.5 and Target Gene Expression in Early-Onset and Severe Preeclampsia". Hypertens Pregnancy. 33 (4): 412–426. doi:10.3109/10641955.2014.925564. PMC 4192008Freely accessible. PMID 24987805.
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