DKK4, or Dickkopf-related protein 4, is a member of the dickkopf family and an inhibitor of the Wnt/β -catenin signalling pathway. The Wnt signal pathway is extensively involved in embryonic development, homeostasis maintenance, and tumor pathogenesis. DKK4 is not only implicated in tumour-related processes such as growth, invasion, migration, and chemotherapy resistance, but also in osteoblastogenesis and secondary hair or meibomian gland formation. It has also been linked to schizophrenia [1].

A Dkk4-Cre knock-in mouse line was generated to study the activation dynamics of Dkk4 in ectodermal appendages. The Dkk4-Cre activity was evident at the prospective sites of ectodermal appendages, overlapping with the Dkk4 mRNA expression. Lineage-tracing suggested that certain mesenchymal cells in the embryo posterior were likely derived from a few Dkk4-Cre-expressing cells in the epiblast at early gastrulation. Analyses of Dkk4-Cre-expressing cells in developing hair follicle epithelial placodes revealed cellular heterogeneity, supporting the positional and transcriptional cellular variability in placodes [2].

In conclusion, DKK4 is a key inhibitor of the Wnt/β-catenin pathway with diverse functions in development and disease. The Dkk4-Cre knock-in mouse model has provided insights into its role in ectodermal appendage morphogenesis, contributing to our understanding of the molecular mechanisms underlying these biological processes.

References:

1. Lou, Xiaoli, Meng, Yuchen, Hou, Yanqiang. 2021. A literature review on function and regulation mechanism of DKK4. In Journal of cellular and molecular medicine, 25, 2786-2794. doi:10.1111/jcmm.16372. https://pubmed.ncbi.nlm.nih.gov/33586359/

2. Khatif, Houda, Bazzi, Hisham. 2023. Generation and characterization of a Dkk4-Cre knock-in mouse line. In Genesis (New York, N.Y. : 2000), 62, e23532. doi:10.1002/dvg.23532. https://pubmed.ncbi.nlm.nih.gov/37435631/