Megf10, short for multiple epidermal growth factor-like domains 10, is a gene with crucial functions in various biological processes. It functions as a phagocytic receptor and is involved in pathways related to synapse remodelling and muscle development [1,2,3]. In the nervous system, it is associated with the MERTK pathway in astrocyte-mediated synapse elimination, which is vital for neural circuit refinement, learning, memory, and understanding neurological diseases [1]. In muscle, it is related to the development and regeneration of skeletal muscle [2,3]. Genetic models, such as Drosophila and mouse models, are valuable for studying Megf10 [3].

In developing mice deficient in astrocyte Megf10 and MERTK pathways, retinogeniculate connections fail to refine normally, and excess functional synapses are retained, highlighting Megf10's role in synapse elimination in the nervous system [1]. Megf10-deficient mouse muscle satellite cells show reduced proliferation and migration, and skeletal muscles have impaired regeneration, indicating its importance in muscle regeneration [2]. In adult Megf10-knockout mice, there is a reduction in excitatory synapse elimination in the hippocampus, leading to defective long-term synaptic plasticity and impaired hippocampal memory formation, further emphasizing its role in maintaining circuit connectivity for cognitive function [6].

In conclusion, Megf10 is essential for synapse remodelling in the nervous system and muscle development and regeneration. The use of gene-knockout mouse models has revealed its significance in these processes, providing insights into neurological diseases and muscle-related disorders such as MEGF10 myopathy [1,2,4,5,6].

References:

1. Chung, Won-Suk, Clarke, Laura E, Wang, Gordon X, Smith, Stephen J, Barres, Ben A. 2013. Astrocytes mediate synapse elimination through MEGF10 and MERTK pathways. In Nature, 504, 394-400. doi:10.1038/nature12776. https://pubmed.ncbi.nlm.nih.gov/24270812/

2. Li, Chengcheng, Vargas-Franco, Dorianmarie, Saha, Madhurima, Pacak, Christina A, Kang, Peter B. 2020. Megf10 deficiency impairs skeletal muscle stem cell migration and muscle regeneration. In FEBS open bio, 11, 114-123. doi:10.1002/2211-5463.13031. https://pubmed.ncbi.nlm.nih.gov/33159715/

3. Draper, Isabelle, Saha, Madhurima, Stonebreaker, Hannah, Matin, Bahar, Kang, Peter B. 2019. The impact of Megf10/Drpr gain-of-function on muscle development in Drosophila. In FEBS letters, 593, 680-696. doi:10.1002/1873-3468.13348. https://pubmed.ncbi.nlm.nih.gov/30802937/

4. Harris, Elizabeth, Marini-Bettolo, Chiara, Töpf, Ana, Bushby, Kate, Straub, Volker. 2017. MEGF10 related myopathies: A new case with adult onset disease with prominent respiratory failure and review of reported phenotypes. In Neuromuscular disorders : NMD, 28, 48-53. doi:10.1016/j.nmd.2017.09.017. https://pubmed.ncbi.nlm.nih.gov/29128256/

5. Saha, Madhurima, Rizzo, Skylar A, Ramanathan, Manashwi, Draper, Isabelle, Kang, Peter B. . Selective serotonin reuptake inhibitors ameliorate MEGF10 myopathy. In Human molecular genetics, 28, 2365-2377. doi:10.1093/hmg/ddz064. https://pubmed.ncbi.nlm.nih.gov/31267131/

6. Lee, Joon-Hyuk, Kim, Ji-Young, Noh, Seulgi, Park, Hyungju, Chung, Won-Suk. 2020. Astrocytes phagocytose adult hippocampal synapses for circuit homeostasis. In Nature, 590, 612-617. doi:10.1038/s41586-020-03060-3. https://pubmed.ncbi.nlm.nih.gov/33361813/