PlexinD1 Glycoprotein Controls Migration of Positively Selected Thymocytes into the Medulla

Choi, Young Il; Duke‐Cohan, Jonathan S.; Ahmed, Wesam; Handley, Maris; Mann, Fanny; Epstein, Jonathan A.; Clayton, Linda K.; Reinherz, Ellis L.

doi:10.1016/j.immuni.2008.10.008

Cited by 117 publications

(160 citation statements)

References 41 publications

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“…47). In particular, Sema3E and PlexinD1 have been reported to play an active role in vascular system development 29,48,49 , but they also control the migration of mouse thymocytes 50 and tumour cells 51 . Indeed, mice lacking Plxnd1 showed impaired thymocyte trafficking 50 and a poorly developed vascular system 29 .…”

Section: Discussionmentioning

confidence: 99%

“…In particular, Sema3E and PlexinD1 have been reported to play an active role in vascular system development 29,48,49 , but they also control the migration of mouse thymocytes 50 and tumour cells 51 . Indeed, mice lacking Plxnd1 showed impaired thymocyte trafficking 50 and a poorly developed vascular system 29 . Today, it is generally accepted that the stereotypical organization of the blood vessels is guided by the same genetic and molecular mechanisms that guide developing axons (reviewed in refs 26,36), although it is only in recent years that the developmental role played by Sema3E/PlexinD1 in the central and peripheral nervous systems began to be elucidated.…”

Section: Discussionmentioning

confidence: 99%

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Sema3E/PlexinD1 regulates the migration of hem-derived Cajal-Retzius cells in developing cerebral cortex

et al. 2014

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During the development of the cerebral cortex, Cajal-Retzius (CR) cells settle in the preplate and coordinate the precise growth of the neocortex. Indeed, CR cells migrate tangentially from specific proliferative regions of the telencephalon (for example, the cortical hem (CH)) to populate the entire cortical surface. This is a very finely tuned process regulated by an emerging number of factors that has been sequentially revealed in recent years. However, the putative participation of one of the major families of axon guidance molecules in this process, the Semaphorins, was not explored. Here we show that Semaphorin-3E (Sema3E) is a natural negative regulator of the migration of PlexinD1-positive CR cells originating in the CH. Our results also indicate that Sema3E/PlexinD1 signalling controls the motogenic potential of CR cells in vitro and in vivo. Indeed, absence of Sema3E/PlexinD1 signalling increased the migratory properties of CR cells. This modulation implies negative effects on CXCL12/CXCR4 signalling and increased ADF/Cofilin activity.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Sema3E/PlexinD1 regulates the migration of hem-derived Cajal-Retzius cells in developing cerebral cortex

et al. 2014

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“…81 In addition, it has been shown that some chemorepellent molecules, including semaphorins and ephrins, affect thymocyte differentiation during their development. [82][83][84] Sema3E, which interacts with plexin-D1 in an NP-1-independent manner, was recently reported to participate in thymocyte development. 82 Plexin-D1 expression is high in CD4 1 CD8 1 thymocytes (double-positive, DP) but decreased in single-positive cells.…”

Section: Semaphorins In the Thymusmentioning

confidence: 99%

“…[82][83][84] Sema3E, which interacts with plexin-D1 in an NP-1-independent manner, was recently reported to participate in thymocyte development. 82 Plexin-D1 expression is high in CD4 1 CD8 1 thymocytes (double-positive, DP) but decreased in single-positive cells. Furthermore, its ligand, Sema3E, is preferentially expressed in the medulla rather than in the cortex.…”

Section: Semaphorins In the Thymusmentioning

confidence: 99%

Regulation of immune cell responses by semaphorins and their receptors

2010

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Semaphorins were originally identified as axon guidance factors involved in the development of the neuronal system. However, accumulating evidence indicates that several members of semaphorins, so-called 'immune semaphorins', are crucially involved in various phases of immune responses. These semaphorins regulate both immune cell interactions and immune cell trafficking during physiological and pathological immune responses. Here, we review the following two functional aspects of semaphorins and their receptors in immune responses: their functions in cell-cell interactions and their involvement in immune cell trafficking.

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“…While studying the molecular interactions controlling mouse thymocyte development, we identified plexinD1 as a critical mediator for thymocytes destined to mature into T lymphocytes populating the mammalian immune system (6). Plxnd1 encoding plexinD1 is transcriptionally regulated at a key intermediate stage of thymocyte development.…”

mentioning

confidence: 99%

Dynamic control of β1 integrin adhesion by the plexinD1-sema3E axis

Choi

Duke‐Cohan

Chen

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Plexins and semaphorins comprise a large family of receptorligand pairs controlling cell guidance in nervous, immune, and vascular systems. How plexin regulation of neurite outgrowth, lymphoid trafficking, and vascular endothelial cell branching is linked to integrin function, central to most directed movement, remains unclear. Here we show that on developing thymocytes, plexinD1 controls surface topology of nanometer-scaled β1 integrin adhesion domains in cis, whereas its ligation by sema3E in trans regulates individual β1 integrin catch bonds. Loss of plexinD1 expression reduces β1 integrin clustering, thereby diminishing avidity, whereas sema3E ligation shortens individual integrin bond lifetimes under force to reduce stability. Consequently, both decreased expression of plexinD1 during developmental progression and a thymic medulla-emanating sema3E gradient enhance thymocyte movement toward the medulla, thus enforcing the orchestrated lymphoid trafficking required for effective immune repertoire selection. Our results demonstrate plexin-tunable molecular features of integrin adhesion with broad implications for many cellular processes.thymocyte development | mechanobiology | integrin activation | autoimmunity | central tolerance I t is well established that plexins and their semaphorin ligands regulate biological processes in multiple physiological domains including axon pathfinding (1, 2), angiogenesis (3), and immunity (4). Although plexins harbor potential for regulating small GTPases that mediate cytoskeletal remodeling, either through a direct cytoplasmic GTPase-activating protein (GAP) domain and Rac/Rho-GTPase binding domain or through sequestration of guanidine nucleotide exchange factor (GEF) proteins to the membrane-proximal cytoplasmic face, there is little consensus on plexin signaling pathways in a complex physiological context (5).While studying the molecular interactions controlling mouse thymocyte development, we identified plexinD1 as a critical mediator for thymocytes destined to mature into T lymphocytes populating the mammalian immune system (6). Plxnd1 encoding plexinD1 is transcriptionally regulated at a key intermediate stage of thymocyte development. Double-negative (DN) thymocytes lacking expression of CD4 and CD8 as well as plexinD1 differentiate in the thymic cortex into largely nondividing CD4 + CD8 + double-positive (DP) thymocytes that display surface αβ T-cell receptors (TCRs) and express plexinD1 (6). Despite being highly mobile (7), DP thymocytes remain sequestered in the cortex in frequent physical association with thymic epithelial cells (TECs), moving toward the thymic medulla via chemokine guidance only subsequent to TCR stimulation by self-derived peptide/MHC complexes (pMHC) that induce CD69 expression and support cell survival, i.e., positive selection (8, 9). CD69 + DP cells differentiate further into CD4 + CD8 − or CD4 − CD8 + singlepositive (SP) thymocytes, translocating to the thymic medulla to complete their maturation (10, 11). While traversing the thymus, immatu...

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PlexinD1 Glycoprotein Controls Migration of Positively Selected Thymocytes into the Medulla

Cited by 117 publications

References 41 publications

Sema3E/PlexinD1 regulates the migration of hem-derived Cajal-Retzius cells in developing cerebral cortex

Sema3E/PlexinD1 regulates the migration of hem-derived Cajal-Retzius cells in developing cerebral cortex

Regulation of immune cell responses by semaphorins and their receptors

Dynamic control of β1 integrin adhesion by the plexinD1-sema3E axis

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