Dcx-KO Mouse

Dcx, also known as doublecortin, is a Microtubule Associated Protein (MAP) [3]. It plays crucial roles in multiple biological processes, such as neural progenitor cell proliferation, radial glial fiber extension, which are essential for normal cortical development. It may be involved in signal transduction through phosphorylation by kinases like JNK, and is associated with pathways such as Wnt signaling, neuron migration, and axon and dendrite morphogenesis [1,3].

In a DCX knockout ferret model, the critical roles of DCX in neural progenitor cell proliferation and radial glial fiber extension were revealed, and disrupted neuronal lamination in lissencephaly was demonstrated, enhancing understanding of the cellular and molecular mechanisms underlying lissencephaly [2]. In mouse models of prostate cancer, selective genetic depletion of DCX+ cells inhibited early tumour development, while transplantation of DCX+ neural progenitors promoted tumour growth and metastasis, indicating a crosstalk between the central nervous system and prostate tumours [4].

In conclusion, Dcx is essential for normal cortical development and is involved in processes like neuron migration. Gene knockout models, such as the DCX knockout ferret and mouse models with manipulation of DCX+ cells, have contributed to understanding its role in diseases like lissencephaly and prostate cancer, providing insights into disease mechanisms and potential treatment targets [2,4].

References:

1. Delprato, Anna, Xiao, Emily, Manoj, Devika. 2022. Connecting DCX, COMT and FMR1 in social behavior and cognitive impairment. In Behavioral and brain functions : BBF, 18, 7. doi:10.1186/s12993-022-00191-7. https://pubmed.ncbi.nlm.nih.gov/35590332/

2. Wang, Wei, Yin, Chonghai, Wen, Shaonan, Wu, Qian, Wang, Xiaoqun. 2024. DCX knockout ferret reveals a neurogenic mechanism in cortical development. In Cell reports, 43, 114508. doi:10.1016/j.celrep.2024.114508. https://pubmed.ncbi.nlm.nih.gov/39018244/

3. Reiner, Orly, Gdalyahu, Amos, Ghosh, Indraneel, Nir, Ronit, Sapir, Tamar. 2004. DCX's phosphorylation by not just another kinase (JNK). In Cell cycle (Georgetown, Tex.), 3, 747-51. doi:. https://pubmed.ncbi.nlm.nih.gov/15118415/

4. Mauffrey, Philippe, Tchitchek, Nicolas, Barroca, Vilma, Roméo, Paul-Henri, Magnon, Claire. 2019. Progenitors from the central nervous system drive neurogenesis in cancer. In Nature, 569, 672-678. doi:10.1038/s41586-019-1219-y. https://pubmed.ncbi.nlm.nih.gov/31092925/