Amalgam regulates the receptor tyrosine kinase pathway through Sprouty in glial cell development in the Drosophila larval brain

• Published in: Journal of cell science Vol. 133; no. 19
• Main Authors: Ariss, Majd M, Terry, Alexander R, Islam, Abul B M M K, Hay, Nissim, Frolov, Maxim V
• Format: Journal Article
• Language: English
• Published: England The Company of Biologists Ltd 01.10.2020
• Subjects: Animals; Brain - metabolism; Drosophila - metabolism; Drosophila Proteins - genetics; Gene Expression Regulation, Developmental; Immunoglobulins - genetics; Larva - metabolism; Membrane Proteins - genetics; Membrane Proteins - metabolism; Neuroglia - metabolism; Receptor Protein-Tyrosine Kinases - genetics; Receptor Protein-Tyrosine Kinases - metabolism; LSAMP; Receptor tyrosine kinase; Single-cell RNA-sequencing; Drosophila; Sprouty; Blood–brain barrier
• ISSN: 1477-9137; 0021-9533; 1477-9137
• DOI: 10.1242/jcs.250837

The receptor tyrosine kinase (RTK) pathway plays an essential role in development and disease by controlling cell proliferation and differentiation. Here, we profile the larval brain by single-cell RNA-sequencing and identify ( ), which encodes a cell adhesion protein of the immunoglobulin IgLON family, as regulating the RTK pathway activity during glial cell development. Depletion of Ama reduces cell proliferation, affects glial cell type composition and disrupts the blood-brain barrier (BBB), which leads to hemocyte infiltration and neuronal death. We show that Ama depletion lowers RTK activity by upregulating Sprouty (Sty), a negative regulator of the RTK pathway. Knockdown of Ama blocks oncogenic RTK signaling activation in the glioma model and halts malignant transformation. Finally, knockdown of a human ortholog of Ama, LSAMP, results in upregulation of SPROUTY2 in glioblastoma cell lines, suggesting that the relationship between Ama and Sty is conserved.