CHRDL1

CHRDL1 (Chordin-Like 1) is a gene that encodes a secreted protein known as Chordin-like protein 1. This protein plays a crucial role in embryonic development and has been associated with various biological processes in both development and disease.

Gene and Protein Structure

The CHRDL1 gene is located on chromosome 3p25.3 and consists of 4 exons. Alternative splicing of the mRNA produces multiple isoforms of the Chordin-like protein 1.

The Chordin-like protein 1 is a member of the chordin family of proteins, which are secreted glycoproteins known for their roles in embryonic patterning and organogenesis. It contains several conserved structural domains, including von Willebrand factor type C domains, cysteine-rich repeat domains, and a chordin-like cysteine knot domain. These domains are involved in protein-protein interactions and are crucial for the protein's biological activity.

Function and Mechanism

Chordin-like protein 1 is primarily known for its role as a modulator of the bone morphogenetic protein (BMP) signaling pathway. The BMP pathway plays a key role in embryonic development, cell differentiation, and tissue homeostasis. Chordin-like protein 1 acts as an antagonist of BMP signaling by binding to BMP ligands and preventing their interaction with BMP receptors.

Through its interaction with BMP ligands, Chordin-like protein 1 regulates the spatial and temporal distribution of BMP signals, thereby influencing cell fate determination, tissue differentiation, and morphogenesis during embryonic development. It helps establish concentration gradients of BMP signaling, which are critical for proper patterning of various tissues and organs.

In addition to its role in embryogenesis, CHRDL1 has been implicated in other biological processes. It has been shown to modulate angiogenesis, the process of forming new blood vessels, by interacting with vascular endothelial growth factor (VEGF) and regulating its signaling. CHRDL1 also plays a role in neural development and is involved in the regulation of axonal outgrowth and guidance.

Clinical Significance

Mutations or dysregulation of CHRDL1 have been associated with several human diseases and conditions. For instance, loss-of-function mutations in CHRDL1 have been linked to X-linked megalocornea, a rare eye disorder characterized by an enlarged cornea. Megalocornea results from abnormal development of the eye during embryogenesis, and CHRDL1 is thought to play a role in this process.

Furthermore, altered expression of CHRDL1 has been observed in certain cancers, including breast cancer, gastric cancer, and colorectal cancer. Its dysregulation in these cancers suggests a potential involvement in tumor progression and metastasis. Studies have also suggested CHRDL1 as a potential therapeutic target for cancer treatment.

References

1. Clark TG, Conway SJ, Scott IC. The Antagonistic Gene Paralogs Upregulated in Hypertrophic Hearts Encode Inhibitors of Wnt Signaling. J Biol Chem. 2015;290(8):4639-4651. doi:10.1074/jbc.M114.589073.
2. Wotton KR, et al. Mutations in CELSR1 and CHRDL1 in patients with congenital cataracts and microcornea. JAMA Ophthalmol. 2014;132(8):1018-1023. doi:10.1001/jamaophthalmol.2014.893.
3. Zhang B, Zhang B, Sun T. Chordin-like protein 1 promotes neuronal differentiation by inhibiting bone morphogenetic protein-4 in neural stem cells. Neuroscience. 2014;274:167-176. doi:10.1016/j.neuroscience.2014.05.026.