ISL1

Insulin gene enhancer protein ISL-1 is a is_associated_with::protein that in humans is encoded by the ISL1 is_associated_with::gene.

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

Interactions
ISL1 has been shown to interact with is_associated_with::Estrogen receptor alpha.

Role in cardiac development
ISL1 is a marker for cardiac progenitors of the is_associated_with::secondary heart field (SHF) which includes the right ventricle and the outflow tract. It also has a biological function as shown in Isl1 knockout mice which have a severely deformed heart. 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: is_associated_with::cardiomyocytes, is_associated_with::smooth muscle and is_associated_with::endothelial cell lineages.

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