Tinman (gene)

Muscle-specific homeobox protein tinman
Identifiers
Organism	Drosophila melanogaster
Symbol	tin
UniProt	P22711
Search for Structures Swiss-model Domains InterPro

tinman, or tin is an Nk2-homeobox containing transcription factor first isolated in Drosophila flies. 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] This gene is named after the character Tin Woodman who lacks a heart, as flies with nonfunctional tinman genes have cardiac deformities.

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.

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. Evans SM, Yan W, Murillo MP, Ponce J, Papalopulu N (November 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 homologue of tinman". Development. 121 (11): 3889–99. doi:10.1242/dev.121.11.3889. PMID 8582297. Retrieved 15 April 2014.
2. Cokkinos DV (2014). Introduction to Translational Cardiovascular Research. Springer. p. 19. ISBN 9783319087986.
3. Fu Y, Ruiz-Lozano P, Evans SM (November 1997). "A rat homeobox gene, rNKx-2.5, is a homologue of the tinman gene in Drosophila and is mainly expressed during heart development". Development Genes and Evolution. 207 (5): 352–358. doi:10.1007/s004270050122. PMID 27747432. S2CID 21534857.
4. Bodmer R (July 1993). "The gene tinman is required for specification of the heart and visceral muscles in Drosophila". Development. 118 (3): 719–29. doi:10.1242/dev.118.3.719. PMID 7915669.
5. "Recent advances in cardiovascular development". Circulation Research. 113 (11): e102-5. November 2013. doi:10.1161/CIRCRESAHA.113.302820. PMID 24201114.
6. Rivers ER, Horton AJ, Hawk AF, Favre EG, Senf KM, Nietert PJ, et al. (November 2014). "Placental Nkx2-5 and target gene expression in early-onset and severe preeclampsia". Hypertension in Pregnancy. 33 (4): 412–26. doi:10.3109/10641955.2014.925564. PMC 4192008. PMID 24987805.