Browsing by Subject "Receptors, Immunologic"

Now showing 1 - 4 of 4

Open Access
Convergent differential regulation of SLIT-ROBO axon guidance genes in the brains of vocal learners.
(J Comp Neurol, 2015-04-15) Wang, Rui; Chen, Chun-Chun; Hara, Erina; Rivas, Miriam V; Roulhac, Petra L; Howard, Jason T; Chakraborty, Mukta; Audet, Jean-Nicolas; Jarvis, Erich D
Only a few distantly related mammals and birds have the trait of complex vocal learning, which is the ability to imitate novel sounds. This ability is critical for speech acquisition and production in humans, and is attributed to specialized forebrain vocal control circuits that have several unique connections relative to adjacent brain circuits. As a result, it has been hypothesized that there could exist convergent changes in genes involved in neural connectivity of vocal learning circuits. In support of this hypothesis, expanding on our related study (Pfenning et al. [2014] Science 346: 1256846), here we show that the forebrain part of this circuit that makes a relatively rare direct connection to brainstem vocal motor neurons in independent lineages of vocal learning birds (songbird, parrot, and hummingbird) has specialized regulation of axon guidance genes from the SLIT-ROBO molecular pathway. The SLIT1 ligand was differentially downregulated in the motor song output nucleus that makes the direct projection, whereas its receptor ROBO1 was developmentally upregulated during critical periods for vocal learning. Vocal nonlearning bird species and male mice, which have much more limited vocal plasticity and associated circuits, did not show comparable specialized regulation of SLIT-ROBO genes in their nonvocal motor cortical regions. These findings are consistent with SLIT and ROBO gene dysfunctions associated with autism, dyslexia, and speech sound language disorders and suggest that convergent evolution of vocal learning was associated with convergent changes in the SLIT-ROBO axon guidance pathway.
Open Access
Microglia are effector cells of CD47-SIRPα antiphagocytic axis disruption against glioblastoma.
(Proceedings of the National Academy of Sciences of the United States of America, 2019-01) Hutter, Gregor; Theruvath, Johanna; Graef, Claus Moritz; Zhang, Michael; Schoen, Matthew Kenneth; Manz, Eva Maria; Bennett, Mariko L; Olson, Andrew; Azad, Tej D; Sinha, Rahul; Chan, Carmel; Assad Kahn, Suzana; Gholamin, Sharareh; Wilson, Christy; Grant, Gerald; He, Joy; Weissman, Irving L; Mitra, Siddhartha S; Cheshier, Samuel H
Glioblastoma multiforme (GBM) is a highly aggressive malignant brain tumor with fatal outcome. Tumor-associated macrophages and microglia (TAMs) have been found to be major tumor-promoting immune cells in the tumor microenvironment. Hence, modulation and reeducation of tumor-associated macrophages and microglia in GBM is considered a promising antitumor strategy. Resident microglia and invading macrophages have been shown to have distinct origin and function. Whereas yolk sac-derived microglia reside in the brain, blood-derived monocytes invade the central nervous system only under pathological conditions like tumor formation. We recently showed that disruption of the SIRPα-CD47 signaling axis is efficacious against various brain tumors including GBM primarily by inducing tumor phagocytosis. However, most effects are attributed to macrophages recruited from the periphery but the role of the brain resident microglia is unknown. Here, we sought to utilize a model to distinguish resident microglia and peripheral macrophages within the GBM-TAM pool, using orthotopically xenografted, immunodeficient, and syngeneic mouse models with genetically color-coded macrophages (Ccr2 ^RFP) and microglia (Cx3cr1 ^GFP). We show that even in the absence of phagocytizing macrophages (Ccr2 ^RFP/RFP), microglia are effector cells of tumor cell phagocytosis in response to anti-CD47 blockade. Additionally, macrophages and microglia show distinct morphological and transcriptional changes. Importantly, the transcriptional profile of microglia shows less of an inflammatory response which makes them a promising target for clinical applications.
Open Access
Phosphorylation of cell surface receptors: a mechanism for regulating signal transduction pathways.
(Endocr Rev, 1988-02) Sibley, DR; Benovic, JL; Caron, MG; Lefkowitz, RJ
Open Access
Robo functions as an attractive cue for glial migration through SYG-1/Neph.
(eLife, 2020-11-19) Qu, Zhongwei; Zhang, Albert; Yan, Dong
As one of the most-studied receptors, Robo plays functions in many biological processes, and its functions highly depend on Slit, the ligand of Robo. Here we uncover a Slit-independent role of Robo in glial migration and show that neurons can release an extracellular fragment of Robo upon cleavage to attract glia during migration in Caenorhabditis elegans. Furthermore, we identified the conserved cell adhesion molecule SYG-1/Neph as a receptor for the cleaved extracellular Robo fragment to mediate glial migration and SYG-1/Neph functions through regulation of the WAVE complex. Our studies reveal a previously unknown Slit-independent function and regulatory mechanism of Robo and show that the cleaved extracellular fragment of Robo can function as a ligand for SYG-1/Neph to guide glial migration. As Robo, the cleaved region of Robo, and SYG-1/Neph are all highly conserved across the animal kingdom, our findings may present a conserved Slit-independent Robo mechanism during brain development.