MEGF8, encoding a multidomain transmembrane protein, is highly conserved across species. It is involved in multiple essential functions such as playing a role in synaptic and mitochondrial functions in the central nervous system [1]. It also modifies BMP signaling in trigeminal sensory neurons, guiding the development of TG axons [3]. Additionally, MEGF8 is associated with Hedgehog and Nodal signaling pathways, which are crucial for embryonic development [7]. Genetic models like Drosophila and mouse models have been valuable for studying its functions [4,5].

Mutations in Megf8 lead to various developmental defects. In mouse models, spatial and temporal deletion studies show that Megf8 has a latent effect on left-right patterning and heart development. Deletion at specific embryonic time points can result in aortic arch artery defects, indicating its role in cardiac development and left-right symmetry establishment [6]. In Drosophila, loss-of-function of the MEGF8 homolog causes disorganized denticle belts, growth arrest, and abnormal bristle formation, highlighting its importance in early development [5].

In conclusion, MEGF8 is essential for multiple biological processes including synaptic function, axon guidance, and left-right patterning during development. Studies using gene knockout or knockdown models in mice and Drosophila have significantly contributed to understanding its role in these processes and in diseases like Carpenter syndrome, which is associated with MEGF8 mutations and characterized by craniosynostosis, polysyndactyly, and other congenital abnormalities [2,4,7].

References:

1. Nakadate, Kazuhiko, Kawakami, Kiyoharu. 2023. Immunohistochemical and Immunoelectron Microscopical Distribution of MEGF8 in the Mouse Central Nervous System. In Cells, 13, . doi:10.3390/cells13010063. https://pubmed.ncbi.nlm.nih.gov/38201267/

2. Watts, Laura M, Bertoli, Marta, Attie-Bitach, Tania, Twigg, Stephen R F, Wilkie, Andrew O M. 2024. The phenotype of MEGF8-related Carpenter syndrome (CRPT2) is refined through the identification of eight new patients. In European journal of human genetics : EJHG, 32, 864-870. doi:10.1038/s41431-024-01624-9. https://pubmed.ncbi.nlm.nih.gov/38760421/

3. Engelhard, Caitlin, Sarsfield, Sarah, Merte, Janna, Sucov, Henry M, Ginty, David D. 2013. MEGF8 is a modifier of BMP signaling in trigeminal sensory neurons. In eLife, 2, e01160. doi:10.7554/eLife.01160. https://pubmed.ncbi.nlm.nih.gov/24052814/

4. Chen, Shuting, Venkatesan, Anand, Lin, Yong Qi, Banerjee, Swati, Bhat, Manzoor A. 2022. Drosophila Homolog of the Human Carpenter Syndrome Linked Gene, MEGF8, Is Required for Synapse Development and Function. In The Journal of neuroscience : the official journal of the Society for Neuroscience, 42, 7016-7030. doi:10.1523/JNEUROSCI.0442-22.2022. https://pubmed.ncbi.nlm.nih.gov/35944997/

5. Lloyd, Deborah L, Toegel, Markus, Fulga, Tudor A, Wilkie, Andrew O M. 2018. The Drosophila homologue of MEGF8 is essential for early development. In Scientific reports, 8, 8790. doi:10.1038/s41598-018-27076-y. https://pubmed.ncbi.nlm.nih.gov/29884872/

6. Wang, Wenfeng, Zheng, Xiaoling, Song, Hejie, Zhang, Min, Zhang, Zhen. 2020. Spatial and temporal deletion reveals a latent effect of Megf8 on the left-right patterning and heart development. In Differentiation; research in biological diversity, 113, 19-25. doi:10.1016/j.diff.2020.03.002. https://pubmed.ncbi.nlm.nih.gov/32203821/

7. Twigg, Stephen R F, Lloyd, Deborah, Jenkins, Dagan, McGowan, Simon J, Wilkie, Andrew O M. 2012. Mutations in multidomain protein MEGF8 identify a Carpenter syndrome subtype associated with defective lateralization. In American journal of human genetics, 91, 897-905. doi:10.1016/j.ajhg.2012.08.027. https://pubmed.ncbi.nlm.nih.gov/23063620/