Biology:ISL1

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Short description: Protein-coding gene in the species Homo sapiens


A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example

Insulin gene enhancer protein ISL-1 is a protein that in humans is encoded by the ISL1 gene.[1] [2]

Function

This gene encodes a transcription factor containing two N-terminal LIM domains and one C-terminal homeodomain. The encoded protein plays an important role in the embryogenesis of pancreatic islets of Langerhans. In mouse embryos, a deficiency of this gene results in failure to undergo neural tube motor neuron differentiation.[2]

Interactions

ISL1 has been shown to interact with Estrogen receptor alpha.[3]

Role in cardiac development

ISL1 is a marker for cardiac progenitors of the secondary heart field (SHF) which includes the right ventricle and the outflow tract. The biological function of ISL1 is demonstrated through ISL1 mutant mice and chick embryos that have altered cell proliferation, survival, and migration of cardiogenic precursors and severe cardiac defects.[4] More recently it has been defined as a marker for a cardiac progenitor cell lineage that is capable of differentiating into all 3 major cell types of the heart: cardiomyocytes, smooth muscle and endothelial cell lineages.[5][6][7] Research has shown that ISL1 promotes differentiation of cardiac cells and a depletion of ISL1 can respecify the cell fate of nascent cardiomyocytes, such as from ventricular to an atrial identity. [8]

The validity of ISL1 as a marker for cardiac progenitor cells has been questioned since some groups have found no evidence that ISL1 cells serve as cardiac progenitors.[9] Furthermore, ISL1 is not restricted to second heart field progenitors in the developing heart, but also labels cardiac neural crest.[10] This paper supports work from the Vilquin group in 2011, which concluded that ISL1 can represent cells from both neural crest and cardiomyocyte lineages.[11] While it has been demonstrated by multiple groups that ISL1-positive cells can indeed differentiate into all 3 major cell types of the heart, their significance in cardiovascular development is still unclear and their clinical relevance has been seriously questioned.

References

  1. ↑ "Isolation of the human LIM/homeodomain gene islet-1 and identification of a simple sequence repeat polymorphism [corrected]". Diabetes 43 (7): 935–941. July 1994. doi:10.2337/diabetes.43.7.935. PMID 7912209. 
  2. ↑ 2.0 2.1 "Entrez Gene: ISL1 ISL1 transcription factor, LIM/homeodomain, (islet-1)". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3670. 
  3. ↑ "The LIM/homeodomain protein islet-1 modulates estrogen receptor functions". Molecular Endocrinology 14 (10): 1627–1648. October 2000. doi:10.1210/mend.14.10.0538. PMID 11043578. 
  4. ↑ "Isl1 identifies a cardiac progenitor population that proliferates prior to differentiation and contributes a majority of cells to the heart". Developmental Cell 5 (6): 877–889. December 2003. doi:10.1016/s1534-5807(03)00363-0. PMID 14667410. 
  5. ↑ "Multipotent embryonic isl1+ progenitor cells lead to cardiac, smooth muscle, and endothelial cell diversification". Cell 127 (6): 1151–1165. December 2006. doi:10.1016/j.cell.2006.10.029. PMID 17123592. 
  6. ↑ "Postnatal isl1+ cardioblasts enter fully differentiated cardiomyocyte lineages". Nature 433 (7026): 647–653. February 2005. doi:10.1038/nature03215. PMID 15703750. Bibcode: 2005Natur.433..647L. 
  7. ↑ "Human ISL1 heart progenitors generate diverse multipotent cardiovascular cell lineages". Nature 460 (7251): 113–117. July 2009. doi:10.1038/nature08191. PMID 19571884. Bibcode: 2009Natur.460..113B. 
  8. ↑ "Revised roles of ISL1 in a hES cell-based model of human heart chamber specification". eLife 7. January 2018. doi:10.7554/eLife.31706. PMID 29337667. 
  9. ↑ "Localization of Islet-1-positive cells in the healthy and infarcted adult murine heart". Circulation Research 110 (10): 1303–1310. May 2012. doi:10.1161/CIRCRESAHA.111.259630. PMID 22427341. 
  10. ↑ "Islet1 derivatives in the heart are of both neural crest and second heart field origin". Circulation Research 110 (7): 922–926. March 2012. doi:10.1161/CIRCRESAHA.112.266510. PMID 22394517. 
  11. ↑ "Distinction between two populations of islet-1-positive cells in hearts of different murine strains". Stem Cells and Development 20 (6): 1043–1052. June 2011. doi:10.1089/scd.2010.0374. PMID 20942609. 

Further reading

External links

This article incorporates text from the United States National Library of Medicine, which is in the public domain.



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