DLL1

Description

The DLL1 (delta like canonical Notch ligand 1) is a protein-coding gene located on chromosome 6.

Delta-like protein 1 is a protein that in humans is encoded by the DLL1 gene.

== Function == DLL1 is a human homolog of the Notch Delta ligand and is a member of the delta/serrate/jagged family. It plays a role in mediating cell fate decisions during hematopoiesis. It may play a role in cell-to-cell communication.

DLL1, also known as Drosophila Delta homolog 1, is a transmembrane ligand protein that interacts with NOTCH1, NOTCH2, and NOTCH3 receptors. It binds to the extracellular domain (ECD) of Notch receptors in both cis and trans fashions. Trans-interaction triggers a series of events, including ligand ubiquitination, EPN1 interaction, and actin polymerization, leading to Notch receptor extracellular domain (NECD) transendocytosis. This process activates Notch signaling, resulting in cleavage, hyperphosphorylation, and nuclear accumulation of the Notch intracellular domain (NICD). DLL1 plays a crucial role in embryonic development and the maintenance of adult stem cells in various tissues and the immune system. Its signaling pathway regulates cell lineage, specification, patterning, and morphogenesis by affecting differentiation and proliferation. DLL1 is involved in brain development by regulating neuronal differentiation of neural precursor cells via cell-cell interaction, likely through the lateral inhibitory system. During neocortex development, DLL1-Notch signaling is mediated by dynamic interactions between intermediate neurogenic progenitors and radial glia. This signaling is essential for Bergmann glial monolayer formation and morphological maturation during cerebellar development. In the retina and spinal cord, DLL1 regulates neurogenesis by preventing premature differentiation of neural progenitors and maintaining progenitors in the spinal cord. It also controls neurogenesis in the neural tube along the dorsoventral axis, maintaining quiescence of neural stem cells and acting as a fate determinant. DLL1 is involved in immune system development, particularly in the development of all T-cells and marginal zone (MZ) B-cells. It blocks progenitor cell differentiation into the B-cell lineage while promoting the emergence of T-cell/NK-cell precursor cells. DLL1 is also involved in muscle development, inhibiting myoblasts differentiation during early development and later regulating progenitor cell differentiation. It modulates cell adhesion and basal lamina formation in satellite cells, maintaining myogenic progenitors by suppressing differentiation. During craniofacial and trunk myogenesis, it suppresses differentiation of cranial mesoderm-derived and somite-derived muscle. DLL1 plays a role in pancreatic cell development, potentially initiating proximodistal patterning in the early pancreatic epithelium. It stimulates multipotent pancreatic progenitor cell proliferation and pancreatic growth. In fetal development, DLL1 maintains arterial identity and the responsiveness of arterial endothelial cells to VEGFA. It also controls sprouting angiogenesis and vertical branch formation. DLL1 negatively regulates goblet cell differentiation in the intestine and controls secretory fat commitment. It is involved in inner ear development, negatively regulating auditory hair cell differentiation, and plays a role in nephron development through Notch signaling. DLL1 regulates growth, blood pressure, and energy homeostasis.

DLL1 is also known as DELTA1, DL1, Delta, NEDBAS.

Associated Diseases

WES Whole Exome Sequencing

Clinical Exome Sequencing