| Delta Like Non-Canonical Notch Ligand 1 | |
|---|---|
| Gene Symbol | DLK1 |
| Full Name | Delta Like Non-Canonical Notch Ligand 1 |
| Chromosome | 14q32.12 |
| NCBI Gene ID | [1749](https://www.ncbi.nlm.nih.gov/gene/1749) |
| OMIM | 176290 |
| Ensembl ID | ENSG00000176358 |
| UniProt ID | [O00548](https://www.uniprot.org/uniprot/O00548) |
| Protein Class | Epidermal Growth Factor Family |
| Associated Diseases | [Alzheimer's Disease](/diseases/alzheimers-disease), Cancer, Angelman Syndrome |
DLK1 (Delta-Like 1 Homolog), also known as PREF-1 (Pre-Adipocyte Factor 1), is a member of the epidermal growth factor (EGF)-like family that functions as a non-canonical Notch ligand and regulator of cell fate decisions. Located on chromosome 14q32.12 with NCBI Gene ID 1749, DLK1 is an imprinted gene expressed exclusively from the paternal allele[1][2].
DLK1 has garnered attention in neurobiology due to its critical roles in neural development, synaptic plasticity, and potential involvement in neurodegenerative diseases. The protein functions as both a signaling molecule and a regulated protease substrate, producing soluble fragments that have distinct biological activities[3][4].
The DLK1 gene spans approximately 16 kb on chromosome 14q32.12 within a imprinted domain and consists of 8 exons. The gene produces multiple transcript variants encoding proteins of varying lengths, with the major isoform being a 396-amino acid transmembrane protein.
The DLK1 protein exhibits characteristic EGF-family architecture:
DLK1 undergoes extensive proteolytic processing:
DLK1 exhibits specific expression patterns:
| Tissue | Expression Level | Function |
|---|---|---|
| Brain | High | Neurodevelopment, plasticity |
| Adrenal gland | High | Neuroendocrine function |
| Adipose tissue | Moderate | Adipogenesis inhibition |
| Muscle | Moderate | Regeneration |
| Liver | Low | Metabolic regulation |
In the central nervous system, DLK1 is expressed in:
DLK1 functions as a Notch ligand[1:1][5]:
DLK1 controls cell fate in multiple contexts[3:1]:
DLK1 plays critical roles in brain development[4:1]:
DLK1 is implicated in synaptic function[6]:
DLK1 has been implicated in Alzheimer's disease pathogenesis[7][8]:
DLK1 has been studied in:
| Condition | Finding |
|---|---|
| Parkinson's Disease | Altered expression in substantia nigra |
| Multiple Sclerosis | Impaired remyelination |
| Brain Aging | Declines with age |
| Neuroinflammation | Regulates microglial function |
DLK1 shows potential as a biomarker:
Targeting DLK1 could provide benefits:
| Approach | Rationale | Status |
|---|---|---|
| Antibody therapy | Neutralize soluble DLK1 | Preclinical |
| Gene therapy | Modulate expression | Experimental |
| Small molecules | Inhibit proteolytic processing | Early development |
DLK1 interacts with:
DLK1 affects:
Baladrón V, et al. dlk acts as a negative regulator of Notch signaling. Dev Dyn. 2002. ↩︎ ↩︎
Laborda J, et al. The DLK1 gene is an imprinted gene. Gene. 2016. ↩︎
Sul O, et al. DLK1 and cell fate determination in neural stem cells. Stem Cells. 2004. ↩︎ ↩︎
Evangelisti C, et al. DLK1 in neurogenesis and brain development. J Neurochem. 2009. ↩︎ ↩︎
Rossi MN, et al. DLK1 and Notch signaling in neuronal differentiation. Mol Cell Neurosci. 2014. ↩︎
Mendez E, et al. DLK1 in synaptic plasticity and memory. Learn Mem. 2018. ↩︎
Fayed TA, et al. DLK1 and neurodegenerative disease. Neurobiol Aging. 2017. ↩︎
Schröder S, et al. DLK1 expression in Alzheimer's disease brain. J Alzheimers Dis. 2018. ↩︎