Cntn2, also known as Contactin-2 or TAG-1, is a cell adhesion molecule of the immunoglobulin superfamily. It is involved in crucial biological processes such as axon guidance, neuronal migration, and fasciculation. CNTN2 may function in pathways related to neural development and neural circuit formation [1,2]. Genetic models, like mouse models, are valuable for studying its functions.

In a mouse model where CNTN2+ pyramidal neurons were ablated during development, significant defects were observed. These included a smaller cortex, reduction of corticothalamic axons, and callosal and commissural defects, suggesting CNTN2's importance in neocortical size determination and axonal tract formation [2]. In Drosophila, loss of CNTN2, a predicted protective modifier, rescued loss of PIGA in a PIGA-CDG model, as well as patient-relevant phenotypes like seizures and climbing defects, indicating its role as a potential genetic modifier in this ultra-rare congenital disorder [3].

In conclusion, Cntn2 is essential for neural development processes such as axon guidance, neuronal migration, and fasciculation. Mouse and Drosophila models have revealed its significance in neocortical development and as a genetic modifier in PIGA-CDG. These model-based studies contribute to understanding its role in neurodevelopmental and related disorders.

References:

1. Fan, Shanghua, Liu, Jianfang, Chofflet, Nicolas, Ren, Gang, Rudenko, Gabby. 2024. Molecular mechanism of contactin 2 homophilic interaction. In Structure (London, England : 1993), 32, 1652-1666.e8. doi:10.1016/j.str.2024.06.004. https://pubmed.ncbi.nlm.nih.gov/38968938/

2. Kastriti, Maria Eleni, Stratigi, Aikaterini, Mariatos, Dimitris, Adameyko, Igor, Karagogeos, Domna. 2019. Ablation of CNTN2+ Pyramidal Neurons During Development Results in Defects in Neocortical Size and Axonal Tract Formation. In Frontiers in cellular neuroscience, 13, 454. doi:10.3389/fncel.2019.00454. https://pubmed.ncbi.nlm.nih.gov/31749685/

3. Thorpe, Holly J, Pedersen, Brent S, Dietze, Miranda, Thomas, Ashley, Chow, Clement Y. 2024. Identification of CNTN2 as a genetic modifier of PIGA-CDG through pedigree analysis of a family with incomplete penetrance and functional testing in Drosophila. In bioRxiv : the preprint server for biology, , . doi:10.1101/2024.08.12.607501. https://pubmed.ncbi.nlm.nih.gov/39211166/