Protein delta homolog 1, also known as delta like non-canonical Notch ligand 1, fetal antigen 1, or preadipocyte factor 1, is a protein encoded by the DLK1 gene in humans. This protein contains multiple epidermal growth factor repeats and functions as a regulator of cell growth. It is a fundamental component involved in various biological processes throughout the body.
Understanding DLK1’s Biological Roles
DLK1 plays a role in regulating the formation of fat cells, a process known as adipogenesis. It exists as a transmembrane protein, but a soluble form, known as Pref-1, is separated from the cell surface by the enzyme ADAM17. This soluble form actively prevents the maturation of pre-adipocytes into adult fat cells, thereby inhibiting adipocyte differentiation. Its influence extends to visceral fat development, where it is linked to the formation of new blood vessels in the peritoneum.
This protein also participates in the broader regulation of cell growth and the differentiation of various cell types. It guides the development of lineages originating from the mesoderm and ectoderm, two fundamental layers of embryonic tissue.
DLK1 has an impact on bone metabolism, functioning as a regulator of bone mass. It works to prevent the formation of new bone while encouraging the breakdown of existing bone tissue. DLK1 also influences neurogenesis, the process of forming new neurons. Studies indicate that appropriate levels of Dlk1 regulate hippocampal neurogenesis, which in turn affects cognitive functions.
The Unique Regulation of DLK1
The DLK1 gene is subject to a distinctive regulatory mechanism known as genomic imprinting. This epigenetic process means that the expression of the gene is determined by its parental origin, rather than being expressed equally from both inherited copies. Specifically, DLK1 is an imprinted gene that is primarily expressed from the paternal allele.
This precise regulation is controlled by its location within the Dlk1-DIO3 imprinting control region, found on human chromosome 14q32. This region is responsible for ensuring that the paternal copy of the gene is the one that is active. Such allele-specific expression is important for maintaining the correct dosage of the DLK1 protein, which is necessary for proper development.
DLK1 is classified as a member of the EGF-like family of homeotic proteins, characterized by the presence of epidermal growth factor-like repeats within its structure. This family classification provides insight into its potential interactions and signaling pathways. The precise control over DLK1 expression through imprinting highlights its specialized functional requirements in the body.
DLK1’s Impact on Health
Dysregulation of DLK1 is linked to certain genetic disorders, including specific forms of precocious puberty. It is associated with Genetic Central Precocious Puberty in males, and potentially in females as well. Another condition tied to DLK1 is Kagami-Ogata syndrome, which can arise from issues such as maternal 14q32.2 hypermethylation, microdeletion, or paternal uniparental disomy of chromosome 14.
Beyond these genetic conditions, DLK1 has been implicated in other health concerns. The soluble form of DLK1 has been observed to promote the growth of gliomas, a type of brain tumor. DLK1 also plays a role in the progression of liver fibrogenesis, a process involving the scarring of liver tissue.
DLK1 influences the proliferation and differentiation of cells within the intestinal lining. Its presence has also been noted in certain types of neuroendocrine lung tumor tissue. Given its established role in inhibiting adipogenesis, alterations in DLK1 function could also have implications for various metabolic disorders.