ISL1

Last updated
ISL1
Protein ISL1 PDB 1bw5.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases ISL1 , ISLET1, Isl-1, ISL LIM homeobox 1
External IDs OMIM: 600366 MGI: 101791 HomoloGene: 1661 GeneCards: ISL1
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_002202

NM_021459

RefSeq (protein)

NP_002193

NP_067434

Location (UCSC) Chr 5: 51.38 – 51.39 Mb Chr 13: 116.43 – 116.45 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Insulin gene enhancer protein ISL-1 is a protein that in humans is encoded by the ISL1 gene. [5] [6]

Contents

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. [6]

Interactions

ISL1 has been shown to interact with Estrogen receptor alpha. [7]

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. [8] 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. [9] [10] [11] 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. [12]

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. [13] Furthermore, ISL1 is not restricted to second heart field progenitors in the developing heart, but also labels cardiac neural crest. [14] This paper supports work from the Vilquin group in 2011, which concluded that ISL1 can represent cells from both neural crest and cardiomyocyte lineages. [15] 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.

Related Research Articles

Transdifferentiation, also known as lineage reprogramming, is the process in which one mature somatic cell is transformed into another mature somatic cell without undergoing an intermediate pluripotent state or progenitor cell type. It is a type of metaplasia, which includes all cell fate switches, including the interconversion of stem cells. Current uses of transdifferentiation include disease modeling and drug discovery and in the future may include gene therapy and regenerative medicine. The term 'transdifferentiation' was originally coined by Selman and Kafatos in 1974 to describe a change in cell properties as cuticle producing cells became salt-secreting cells in silk moths undergoing metamorphosis.

<span class="mw-page-title-main">PAX3</span> Paired box gene 3

The PAX3 gene encodes a member of the paired box or PAX family of transcription factors. The PAX family consists of nine human (PAX1-PAX9) and nine mouse (Pax1-Pax9) members arranged into four subfamilies. Human PAX3 and mouse Pax3 are present in a subfamily along with the highly homologous human PAX7 and mouse Pax7 genes. The human PAX3 gene is located in the 2q36.1 chromosomal region, and contains 10 exons within a 100 kb region.

<span class="mw-page-title-main">HNF1A</span> Protein-coding gene in the species Homo sapiens

HNF1 homeobox A, also known as HNF1A, is a human gene on chromosome 12. It is ubiquitously expressed in many tissues and cell types. The protein encoded by this gene is a transcription factor that is highly expressed in the liver and is involved in the regulation of the expression of several liver-specific genes. Mutations in the HNF1A gene have been known to cause diabetes. The HNF1A gene also contains a SNP associated with increased risk of coronary artery disease.

<span class="mw-page-title-main">PDX1</span> A protein involved in the pancreas and duodenum differentiation

PDX1, also known as insulin promoter factor 1, is a transcription factor in the ParaHox gene cluster. In vertebrates, Pdx1 is necessary for pancreatic development, including β-cell maturation, and duodenal differentiation. In humans this protein is encoded by the PDX1 gene, which was formerly known as IPF1. The gene was originally identified in the clawed frog Xenopus laevis and is present widely across the evolutionary diversity of bilaterian animals, although it has been lost in evolution in arthropods and nematodes. Despite the gene name being Pdx1, there is no Pdx2 gene in most animals; single-copy Pdx1 orthologs have been identified in all mammals. Coelacanth and cartilaginous fish are, so far, the only vertebrates shown to have two Pdx genes, Pdx1 and Pdx2.

<span class="mw-page-title-main">PBX1</span> Protein found in humans

Pre-B-cell leukemia transcription factor 1 is a protein that in humans is encoded by the PBX1 gene. The homologous protein in Drosophila is known as extradenticle, and causes changes in embryonic development.

<span class="mw-page-title-main">Homeobox protein Nkx-2.5</span> Protein-coding gene in humans

Homeobox protein Nkx-2.5 is a protein that in humans is encoded by the NKX2-5 gene.

<span class="mw-page-title-main">HHEX</span> Protein-coding gene in the species Homo sapiens

Hematopoietically-expressed homeobox protein HHEX is a protein that in humans is encoded by the HHEX gene and also known as Proline Rich Homeodomain protein PRH.

<span class="mw-page-title-main">LHX3</span> Protein-coding gene in the species Homo sapiens

LIM/homeobox protein Lhx3 is a protein that in humans is encoded by the LHX3 gene.

Neurogenins, often abbreviated as Ngn, are a family of bHLH transcription factors involved in specifying neuronal differentiation. The family consisting of Neurogenin-1, Neurogenin-2, and Neurogenin-3, plays a fundamental role in specifying neural precursor cells and regulating the differentiation of neurons during embryonic development. It is one of many gene families related to the atonal gene in Drosophila. Other positive regulators of neuronal differentiation also expressed during early neural development include NeuroD and ASCL1.

<span class="mw-page-title-main">LMX1A</span> Protein-coding gene in the species Homo sapiens

LIM homeobox transcription factor 1, alpha, also known as LMX1A, is a protein which in humans is encoded by the LMX1A gene.

<span class="mw-page-title-main">NKX2-2</span> Protein-coding gene in the species Homo sapiens

Homeobox protein Nkx-2.2 is a protein that in humans is encoded by the NKX2-2 gene.

<span class="mw-page-title-main">NKX2-3</span> Protein-coding gene in the species Homo sapiens

Homeobox protein Nkx-2.3 is a protein that in humans is encoded by the NKX2-3 gene.

<span class="mw-page-title-main">Adipogenesis</span>

Adipogenesis is the formation of adipocytes from stem cells. It involves 2 phases, determination, and terminal differentiation. Determination is mesenchymal stem cells committing to the adipocyte precursor cells, also known as preadipocytes which lose the potential to differentiate to other types of cells such as chondrocytes, myocytes, and osteoblasts. Terminal differentiation is that preadipocytes differentiate into mature adipocytes. Adipocytes can arise either from preadipocytes resident in adipose tissue, or from bone-marrow derived progenitor cells that migrate to adipose tissue.

<span class="mw-page-title-main">Neurogenin-3</span> Mammalian protein found in Homo sapiens

Neurogenin-3 (NGN3) is a protein that in humans is encoded by the Neurog3 gene.

<span class="mw-page-title-main">NKX6-1</span> Protein-coding gene in the species Homo sapiens

Homeobox protein Nkx-6.1 is a protein that in humans is encoded by the NKX6-1 gene.

Endogenous cardiac stem cells (eCSCs) are tissue-specific stem progenitor cells harboured within the adult mammalian heart. It has to be noted that a scientific-misconduct scandal, involving Harvard professor Piero Anversa, might indicate that the heart stem cell concept be broken. Therefore, the following article should be read with caution, as it builds on Anversa's results.

In molecular biology, the LIM domain-binding protein family is a family of proteins which binds to the LIM domain of LIM homeodomain proteins which are transcriptional regulators of development.

Neural crest cells are multipotent cells required for the development of cells, tissues and organ systems. A subpopulation of neural crest cells are the cardiac neural crest complex. This complex refers to the cells found amongst the midotic placode and somite 3 destined to undergo epithelial-mesenchymal transformation and migration to the heart via pharyngeal arches 3, 4 and 6.

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. This gene is named after the character Tin Woodman who lacks a heart, as flies with nonfunctional tinman genes have cardiac deformities.

<span class="mw-page-title-main">Pancreatic progenitor cell</span>

Pancreatic progenitor cells are multipotent stem cells originating from the developing fore-gut endoderm which have the ability to differentiate into the lineage specific progenitors responsible for the developing pancreas.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000016082 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000042258 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. Tanizawa Y, Riggs AC, Dagogo-Jack S, Vaxillaire M, Froguel P, Liu L, et al. (July 1994). "Isolation of the human LIM/homeodomain gene islet-1 and identification of a simple sequence repeat polymorphism [corrected]". Diabetes. 43 (7): 935–941. doi:10.2337/diabetes.43.7.935. PMID   7912209.
  6. 1 2 "Entrez Gene: ISL1 ISL1 transcription factor, LIM/homeodomain, (islet-1)".
  7. Gay F, Anglade I, Gong Z, Salbert G (October 2000). "The LIM/homeodomain protein islet-1 modulates estrogen receptor functions". Molecular Endocrinology. 14 (10): 1627–1648. doi: 10.1210/mend.14.10.0538 . PMID   11043578.
  8. Cai CL, Liang X, Shi Y, Chu PH, Pfaff SL, Chen J, Evans S (December 2003). "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. doi:10.1016/s1534-5807(03)00363-0. PMC   5578462 . PMID   14667410.
  9. Moretti A, Caron L, Nakano A, Lam JT, Bernshausen A, Chen Y, et al. (December 2006). "Multipotent embryonic isl1+ progenitor cells lead to cardiac, smooth muscle, and endothelial cell diversification". Cell. 127 (6): 1151–1165. doi: 10.1016/j.cell.2006.10.029 . PMID   17123592. S2CID   31238870.
  10. Laugwitz KL, Moretti A, Lam J, Gruber P, Chen Y, Woodard S, et al. (February 2005). "Postnatal isl1+ cardioblasts enter fully differentiated cardiomyocyte lineages". Nature. 433 (7026): 647–653. Bibcode:2005Natur.433..647L. doi:10.1038/nature03215. PMC   5578466 . PMID   15703750.
  11. Bu L, Jiang X, Martin-Puig S, Caron L, Zhu S, Shao Y, et al. (July 2009). "Human ISL1 heart progenitors generate diverse multipotent cardiovascular cell lineages". Nature. 460 (7251): 113–117. Bibcode:2009Natur.460..113B. doi:10.1038/nature08191. PMID   19571884. S2CID   801804.
  12. Quaranta R, Fell J, Rühle F, Rao J, Piccini I, Araúzo-Bravo MJ, et al. (January 2018). "Revised roles of ISL1 in a hES cell-based model of human heart chamber specification". eLife. 7. doi: 10.7554/eLife.31706 . PMC   5770158 . PMID   29337667.
  13. Weinberger F, Mehrkens D, Friedrich FW, Stubbendorff M, Hua X, Müller JC, et al. (May 2012). "Localization of Islet-1-positive cells in the healthy and infarcted adult murine heart". Circulation Research. 110 (10): 1303–1310. doi:10.1161/CIRCRESAHA.111.259630. PMC   5559221 . PMID   22427341.
  14. Engleka KA, Manderfield LJ, Brust RD, Li L, Cohen A, Dymecki SM, Epstein JA (March 2012). "Islet1 derivatives in the heart are of both neural crest and second heart field origin". Circulation Research. 110 (7): 922–926. doi:10.1161/CIRCRESAHA.112.266510. PMC   3355870 . PMID   22394517.
  15. Khattar P, Friedrich FW, Bonne G, Carrier L, Eschenhagen T, Evans SM, et al. (June 2011). "Distinction between two populations of islet-1-positive cells in hearts of different murine strains". Stem Cells and Development. 20 (6): 1043–1052. doi:10.1089/scd.2010.0374. PMC   5880329 . PMID   20942609.

Further reading

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