Mouse Delta Like Protein 1, DLL1 ELI

Transmembrane ligand protein of NOTCH1, NOTCH2 and NOTCH3 receptors that binds the extracellular domain (ECD) of Notch receptor in a cis and trans fashion manner (PubMed: 21985982, PubMed: 10958687).

Following transinteraction, ligand cells produce mechanical force that depends of a clathrin-mediated endocytosis, requiring ligand ubiquitination, EPN1 interaction, and actin polymerisation; these events promote Notch receptor extracellular domain (NECD) transendocytosis and triggers Notch signaling through induction of cleavage, hyperphosphorylation, and nuclear accumulation of the intracellular domain of Notch receptors (NICD) (PubMed: 10958687, PubMed: 18676613).

Is required for embryonic development and maintenance of adult stem cells in many different tissues and immune systeme; the DLL1-induced Notch signaling is mediated through an intercellular communication that regulates cell lineage, cell specification, cell patterning and morphogenesis through effects on differentiation and proliferation (PubMed: 1719$475.00|$350.009, PubMed: 19562077, PubMed: 18997111, PubMed: 23695674, PubMed: 16495313, PubMed: 21238454, PubMed: 22282195, PubMed: 7671806, PubMed: 17960184, PubMed: 22529374, PubMed: 19389377, PubMed: 23699523, PubMed: 1914$498.00|$360.009, PubMed: 23688253, PubMed: 23806616, PubMed: 26114479, PubMed: 22940113, PubMed: 25220152, PubMed: 20081190, PubMed: 21572390, PubMed: 22096075).

Plays a role in brain development at different level, namely by regulating neuronal differentiation of neural precursor cells via cell-cell interaction, most likely through the lateral inhibitory system in an endogenous level dependent-manner (PubMed: 7671806, PubMed: 18997111).

During neocortex development, Dll1-Notch signaling transmission is mediated by dynamic interactions between intermediate neurogenic progenitors and radial glia; the cell-cell interactions are mediated via dynamic and transient elongation processes, likely to reactivate/maintain Notch activity in neighboring progenitors, and coordinate progenitor cell division and differentiation across radial and zonal boundaries (PubMed: 23699523).

During cerebellar development, regulates Bergmann glial monolayer formation and its morphological maturation through a Notch signaling pathway (PubMed: 23688253).

At the retina and spinal cord level, regulates neurogenesis by preventing the premature differentiation of neural progenitors and also by maintaining progenitors in spinal cord through Notch signaling pathway (PubMed: 19389377, PubMed: 26114479).

Also controls neurogenesis of the neural tube in a progenitor domain-specific fashion along the dorsoventral axis (PubMed: 20081190).

Maintains quiescence of neural stem cells and plays a role as a fate determinant that segregates asymmetrically to one daughter cell during neural stem cells mitosis, resulting in neuronal differentiation in Dll1-inheriting cell (PubMed: 23695674).

Plays a role in immune systeme development, namely the development of all T-cells and marginal zone (MZ) B cells (PubMed: 15146182, PubMed: 19217325).

Blocks the differentiation of progenitor cells into the B-cell lineage while promoting the emergence of a population of cells with the characteristics of a T-cell/NK-cell precursor (By similarity).

Upon MMP14 cleavage, negatively regulates Notch signaling in haematopoietic progenitor cells to specifically maintain normal B-cell development in bone marrow (PubMed: 21572390).

Also plays a role during muscle development.

During early development, inhibits myoblasts differentiation from the medial dermomyotomal lip and later regulates progenitor cell differentiation (PubMed: 1719$475.00|$350.009).

Directly modulates cell adhesion and basal lamina formation in satellite cells through Notch signaling.

Maintains myogenic progenitors pool by suppressing differentiation through down-regulation of MYOD1 and is required for satellite cell homing and PAX7 expression (PubMed: 22940113).

During craniofacial and trunk myogenesis suppresses differentiation of cranial mesoderm-derived and somite-derived muscle via MYOD1 regulation but in cranial mesoderm-derived progenitors, is neither required for satellite cell homing nor for PAX7 expression (PubMed: 25220152).

Also plays a role during pancreatic cell development.

During type B pancreatic cell development, may be involved in the initiation of proximodistal patterning in the early pancreatic epithelium (PubMed: 22529374).

Stimulates multipotent pancreatic progenitor cells proliferation and pancreatic growth by maintaining HES1 expression and PTF1A protein levels (PubMed: 22096075).

During fetal stages of development, is required to maintain arterial identity and the responsiveness of arterial endothelial cells for VEGFA through regulation of KDR activation and NRP1 expression (PubMed: 1914$498.00|$360.009).

Controls sprouting angiogenesis and subsequent vertical branch formation througth regulation on tip cell differentiation (PubMed: 22282195).

Negatively regulates goblet cell differentiation in intestine and controls secretory fat commitment through lateral inhibition in small intestine (PubMed: 21238454, PubMed: 21915337).

Plays a role during inner ear development; negatively regulates auditory hair cell differentiation (PubMed: 16495313).

Plays a role during nephron development through Notch signaling pathway (PubMed: 23806616).

Regulates growth, blood pressure and energy homeostasis (PubMed: 19562077).