N-syndecan deficiency impairs neural migration in brain

N-syndecan (syndecan-3) is a transmembrane proteoglycan that is abundantly expressed in the major axonal pathways and in the migratory routes of the developing brain. When ligated by heparin-binding (HB) growth-associated molecule (GAM; pleiotrophin), N-syndecan mediates cortactin–Src kinase-dependent neurite outgrowth. However, the functional role of N-syndecan in brain development remains unexplored. In this study, we show that N-syndecan deficiency perturbs the laminar structure of the cerebral cortex as a result of impaired radial migration. In addition, neural migration in the rostral migratory stream is impaired in the N-syndecan–null mice. We suggest that the migration defect depends on impaired HB-GAM–induced Src kinase activation and haptotactic migration. Furthermore, we show that N-syndecan interacts with EGF receptor (EGFR) at the plasma membrane and is required in EGFR-induced neuronal migration.

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Role of the EGFR/Ras/Raf pathway in specification of photoreceptor cells in the Drosophila retina

Development ◽

10.1242/dev.128.7.1183 ◽

2001 ◽

Vol 128 (7) ◽

pp. 1183-1191 ◽

Cited By ~ 3

Author(s):

L. Yang ◽

N.E. Baker

Keyword(s):

Map Kinase ◽

Egf Receptor ◽

Eye Development ◽

Photoreceptor Cells ◽

Cell Types ◽

Cell Specification ◽

Kinase Activation ◽

Cell Spacing ◽

Egfr Activation

The Drosophila EGF receptor is required for differentiation of many cell types during eye development. We have used mosaic analysis with definitive null mutations to analyze the effects of complete absence of EGFR, Ras or Raf proteins during eye development. The Egfr, ras and raf genes are each found to be essential for recruitment of R1-R7 cells. In addition Egfr is autonomously required for MAP kinase activation. EGFR is not essential for R8 cell specification, either alone or redundantly with any other receptor that acts through Ras or Raf, or by activating MAP kinase. As with Egfr, loss of ras or raf perturbs the spacing and arrangement of R8 precursor cells. R8 cell spacing is not affected by loss of argos in posteriorly juxtaposed cells, which rules out a model in which EGFR acts through argos expression to position R8 specification in register between adjacent columns of ommatidia. The R8 spacing role of the EGFR was partially affected by simultaneous deletion of spitz and vein, two ligand genes, but the data suggest that EGFR activation independent of spitz and vein is also involved. The results prove that R8 photoreceptors are specified and positioned by distinct mechanisms from photoreceptors R1-R7.

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Interaction between Drosophila EGF receptor and vnd determines three dorsoventral domains of the neuroectoderm

Development ◽

10.1242/dev.125.18.3625 ◽

1998 ◽

Vol 125 (18) ◽

pp. 3625-3633 ◽

Cited By ~ 5

Author(s):

Y. Yagi ◽

T. Suzuki ◽

S. Hayashi

Keyword(s):

Map Kinase ◽

Receptor Tyrosine Kinase ◽

Egf Receptor ◽

Regulatory Region ◽

Homeobox Gene ◽

Kinase Activation ◽

Intermediate Column ◽

Kinase Signaling Pathway ◽

Map Kinase Signaling Pathway

Neurogenesis in Drosophila melanogaster starts by an ordered appearance of neuroblasts arranged in three columns (medial, intermediate and lateral) in each side of the neuroectoderm. Here we show that, in the intermediate column, the receptor tyrosine kinase DER represses expression of proneural genes, achaete and scute, and is required for the formation of neuroblasts. Most of the early function of DER is likely to be mediated by the Ras-MAP kinase signaling pathway, which is activated in the intermediate column, since a loss of a component of this pathway leads to a phenotype identical to that in DER mutants. MAP-kinase activation was also observed in the medial column where esg and proneural gene expression is unaffected by DER. We found that the homeobox gene vnd is required for the expression of esg and scute in the medial column, and show that vnd acts through the negative regulatory region of the esg enhancer that mediates the DER signal, suggesting the role of vnd is to counteract DER-dependent repression. Thus nested expression of vnd and the DER activator rhomboid is crucial to subdivide the neuroectoderm into the three dorsoventral domains.

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Src tyrosine kinase is the trigger but not the mediator of ischemic preconditioning

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.2001.281.3.h1066 ◽

2001 ◽

Vol 281 (3) ◽

pp. H1066-H1074 ◽

Cited By ~ 34

Author(s):

Reiji Hattori ◽

Hajime Otani ◽

Takamichi Uchiyama ◽

Hiroji Imamura ◽

Jianhua Cui ◽

...

Keyword(s):

Tyrosine Kinase ◽

Ischemic Preconditioning ◽

Tyrosine Kinases ◽

Src Kinase ◽

Src Tyrosine Kinase ◽

Kinase Activation ◽

Rat Hearts ◽

Perfused Rat Hearts ◽

Src Activation

The signal cascade that triggers and mediates ischemic preconditioning (IPC) remains unclear. The present study investigated the role of the Src family of tyrosine kinases in IPC. Isolated and buffer-perfused rat hearts underwent IPC with three cycles of 5-min ischemia and 5-min reperfusion, followed by 30-min ischemia and 120-min reperfusion. The Src tyrosine kinase family-selective inhibitor PP1 was administered between 45 and 30 min before ischemia (early PP1 treatment) or for 15 min before IPC [early PP1-preconditioning (PC) treatment]. PP1 was also administered for 5 min before the sustained ischemia (late PP1 treatment) or after IPC (late PP1-PC treatment). Src kinase was activated after 30 min of ischemia in both the membrane and cytosolic fractions. Src kinase was also activated by IPC but was attenuated after the sustained ischemia. Early and late PP1 treatment inhibited Src activation after the sustained ischemia and reduced infarct size. Early PP1-PC inhibited Src activation after IPC but not after the sustained ischemia and blocked cardioprotection afforded by IPC. Late PP1-PC treatment abrogated IPC-induced activation of Src and protein kinase C (PKC)-ε in the membrane but not in the cytosolic fraction. This treatment modality abrogated Src activation after the sustained ischemia and failed to block cardioprotection afforded by IPC. These results suggest that Src kinase activation mediates ischemic injury but triggers IPC in the position either upstream of or parallel to membrane-associated PKC-ε.

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Nyap1 Regulates Multipolar–Bipolar Transition and Morphology of Migrating Neurons by Fyn Phosphorylation during Corticogenesis

Cerebral Cortex ◽

10.1093/cercor/bhz137 ◽

2019 ◽

Vol 30 (3) ◽

pp. 929-941

Author(s):

Shuzhong Wang ◽

Xuzhao Li ◽

Qianru Zhang ◽

Xuejun Chai ◽

Yi Wang ◽

...

Keyword(s):

Neuronal Migration ◽

Protein Tyrosine Kinase ◽

In Utero Electroporation ◽

Neuronal Morphogenesis ◽

Radial Migration ◽

Downstream Target ◽

Cytoskeletal Regulation ◽

Phosphoinositide 3 Kinase ◽

Precise Role

Abstract The coordination of cytoskeletal regulation is a prerequisite for proper neuronal migration during mammalian corticogenesis. Neuronal tyrosine-phosphorylated adaptor for the phosphoinositide 3-kinase 1 (Nyap1) is a member of the Nyap family of phosphoproteins, which has been studied in neuronal morphogenesis and is involved in remodeling of the actin cytoskeleton. However, the precise role of Nyap1 in neuronal migration remains unknown. Here, overexpression and knockdown of Nyap1 in the embryonic neocortex of mouse by in utero electroporation-induced abnormal morphologies and multipolar–bipolar transitions of migrating neurons. The level of phosphorylated Nyap1 was crucial for neuronal migration and morphogenesis in neurons. Furthermore, Nyap1 regulated neuronal migration as a downstream target of Fyn, a nonreceptor protein-tyrosine kinase that is a member of the Src family of kinases. Importantly, Nyap1 mediated the role of Fyn in the multipolar–bipolar transition of migrating neurons. Taken together, these results suggest that cortical radial migration is regulated by a molecular hierarchy of Fyn via Nyap1.

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