ASCL1

Achaete-scute homolog 1 is a is_associated_with::protein that in humans is encoded by the ASCL1 is_associated_with::gene. Because it was discovered subsequent to studies on its homolog in is_associated_with::Drosophila, the is_associated_with::Achaete-scute complex, it was originally named MASH-1 for mammalian achaete scute homolog-1.

Role in neuronal commitment
Development of the vertebrate nervous system begins when the is_associated_with::neural tube forms in the early is_associated_with::embryo. The neural tube eventually gives rise to the entire is_associated_with::nervous system, but first is_associated_with::neuroblasts must differentiate from the is_associated_with::neuroepithelium of the tube. The neuroblasts are the cells that undergo is_associated_with::mitotic division and produce is_associated_with::neurons. Asc is central to the differentiation of the neuroblasts and the is_associated_with::lateral inhibition mechanism which inherently creates a safety net in the event of damage or death in these incredibly important cells.

Differentiation of the neuroblast begins when the cells of the neural tube express Asc and thus upregulate the expression of Delta, a protein essential to the lateral inhibition pathway of neuronal commitment. Delta can diffuse to neighboring cells and bind to the is_associated_with::Notch receptor, a large transmembrane protein which upon activation undergoes is_associated_with::proteolytic cleavage to release the intracellular domain (Notch-ICD). The Notch-ICD is then free to travel to the nucleus and form a complex with Suppressor of is_associated_with::Hairless (SuH) and Mastermind. This complex acts as is_associated_with::transcription regulator of Asc and accomplishes two important tasks. First, it prevents the expression of factors required for differentiation of the cell into a neuroblast. Secondly, it inhibits the neighboring cell's production of Delta. Therefore, the future neuroblast will be the cell that has the greatest Asc activation in the vicinity and consequently the greatest Delta production that will inhibit the differentiation of neighboring cells. The select group of neuroblasts that then differentiate in the neural tube are thus replaceable because the neuroblast’s ability to suppress differentiation of neighboring cells depends on its own ability to produce Asc. This process of neuroblast differentiation via Asc is common to all animals. Although this mechanism was initially studied in Drosophila, homologs to all proteins in the pathway have been found in vertebrates that have the same is_associated_with::bHLH structure.

Autonomic nervous system development
In addition to its important role in neuroblast formation, Asc also functions to mediate is_associated_with::autonomic nervous system (ANS) formation. Asc was initially suspected to play a role in the ANS when ASCL1 was found expressed in cells surrounding the dorsal is_associated_with::aorta, the is_associated_with::adrenal glands and in the developing is_associated_with::sympathetic chain during a specific stage of development. Subsequent studies of mice genetically altered to be MASH-1 deficient revealed defective development of both sympathetic and parasympathetic is_associated_with::ganglia, the two constituents of the ANS.

Interactions
ASCL1 has been shown to interact with is_associated_with::Myocyte-specific enhancer factor 2A.