Mouse neural crest cells secrete both urokinase-type and tissue-type plasminogen activators <i>in vitro</i>

Menoud, Pierre-Alain; Debrot, Sylvain; Schowing, J

doi:10.1242/dev.106.4.685

“…Subsequent studies by other laboratories showed that mouse NC cells secrete urokinase and tissue plasminogen activators (uPA and tPA) into the culture medium ( Menoud et al, 1989 ) and that uPA promotes chick NC migration in vitro via activation of plasmin and TGFβ signaling ( Brauer and Yee, 1993 ; Agrawal and Brauer, 1996 ). Mutations in the lectin complement pathway gene MASP1/3, encoding for Mannose-associated serine protease-1 and -3, cause 3MC (Mingarelli, Malpuech, Michels and Carnevale) syndrome, a rare autosomal recessive disorder that is characterized by a spectrum of developmental features including craniofacial abnormalities ( Rooryck et al, 2011 ).…”

Section: Discussionmentioning

confidence: 99%

Inhibition of the serine protease HtrA1 by SerpinE2 suggests an extracellular proteolytic pathway in the control of neural crest migration

Pera,

Nilsson-De Moura,

Pomeshchik

et al. 2024

eLife

0

View full text Add to dashboard Cite

Here we present an extracellular proteolytic mechanism involving the serine protease HtrA1 and its inhibitor SerpinE2 in the developing neural crest (NC). Knockdown of SerpinE2 by injected antisense morpholino oligonucleotides did not affect the specification of NC progenitors but instead inhibited the migration of NC cells, causing defects in dorsal fin, melanocyte and craniofacial skeleton formation. Similarly, overexpression of the HtrA1 protease impaired NC cell migration and the formation of NC-derived structures. The phenotype of SerpinE2 knockdown was overcome by concomitant downregulation of HtrA1, indicating that SerpinE2 stimulates NC migration by inhibiting endogenous HtrA1 activity. The HtrA1 protease triggers degradation of the cell surface proteoglycan Syndecan-4 (Sdc4). Microinjection of Sdc4 mRNA partially rescued NC migration defects induced both by HtrA1 upregulation and SerpinE2 downregulation. These epistatic experiments suggest a proteolytic pathway by a double inhibition mechanism: SerpinE2 ┤HtrA1 protease ┤Syndecan-4 → NC cell migration

show abstract

“…Subsequent studies by other laboratories showed that mouse NC cells secrete urokinase and tissue plasminogen activators (uPA and tPA) into the culture medium (Menoud et al, 1989) and that uPA promotes chick NC migration in vitro via activation of plasmin and TGFb signaling (Brauer and Yee, 1993;Agrawal and Brauer, 1996). Mutations in the lectin complement pathway gene MASP1/3, encoding for Mannose-associated serine protease-1 and -3, cause 3MC (Mingarelli, Malpuech, Michels and Carnevale) syndrome, a rare autosomal recessive disorder that is characterized by a spectrum of developmental features including craniofacial abnormalities (Rooryck et al, 2011).…”

Section: Extracellular Proteases In Cell Migrationmentioning

confidence: 99%

Inhibition of the serine protease HtrA1 by SerpinE2 suggests an extracellular proteolytic pathway in the control of neural crest migration

Pera,

Moura,

Pomeshchik

et al. 2023

Preprint

0

View full text Add to dashboard Cite

Here we present an extracellular proteolytic mechanism involving the serine protease HtrA1 and its inhibitor SerpinE2 in the developing neural crest (NC). Knockdown of SerpinE2 by injected antisense morpholino oligonucleotides did not affect the specification of NC progenitors but instead inhibited the migration of NC cells, causing defects in dorsal fin, melanocyte and craniofacial skeleton formation. Similarly, overexpression of the HtrA1 protease impaired NC cell migration and the formation of NC-derived structures. The phenotype of SerpinE2 knockdown was overcome by concomitant downregulation of HtrA1, indicating that SerpinE2 stimulates NC migration by inhibiting endogenous HtrA1 activity. The HtrA1 protease triggers degradation of the cell surface proteoglycan Syndecan-4 (Sdc4). Microinjection of Sdc4 mRNA partially rescued NC migration defects induced both by HtrA1 upregulation and SerpinE2 downregulation. These epistatic experiments suggest a proteolytic pathway by a double inhibition mechanism: SerpinE2 - HtrA1 protease - Syndecan-4 - NC cell migration

show abstract

Urokinase-type plasminogen activator regulates cranial neural crest cell migration in vitro

Agrawal

¹

,

Brauer

²

1996

View full text Add to dashboard Cite

Proper migration and differentiation of neural crest (NC) cells are required for normal development of craniofacial structures, heart and great vessels, sensory and autonomic nervous systems, and other organs within vertebrate embryos. Seriae‐protease inhibitors reduce NC cell migration in vitro, suggesting the extracellular proteases are important mediators of NC cell migration. While plasminogen activator activity levels are high in NC cells relative to other embryonic tissues, its ability to regulate NC cell migration has not been specifically tested in vivo or in vitro. In this study, we show urokinase‐type plasminogen activator (uPA) regulates NC cell migration in vitro through its ability to convert plasminogen to plasmin. Using a transfilter migration assay, NC cell migration was measured in the presence or absence of plasminogen. Our results showed that plasminogen significantly enhanced NC cell migration. This increase could not be attributed to differences in initial NC cell attachment or cytotoxicity and did not require a chemotactic gradient. The plasminogen‐enhanced NC cell migration was blocked by aprotinin (a plasmin inhibitor) and was mimicked by the direct addition of plasmin to the NC cells, indicating that the plasminogen effect was mediated through plasmin generation. Furthermore, anticatalytic‐uPA anti‐body blocked the plasminogen‐enhanced NC cell migration showing that NC cell‐associated uPA activity was required for this effect. Finally, decreasing NC‐uPA activity by treating cells with transforming growth factor‐β, also blocked the plasminogen‐dependent increase in cell migration. These data show that in vitro, NC cell migration is regulated by NC‐associated uPA activity suggesting that growth factor‐regulation of this activity may play a major role in regulating NC cell migratory capacity in vivo. © 1996 Wiley‐Liss, Inc.

show abstract

Mouse neural crest cells secrete both urokinase-type and tissue-type plasminogen activators in vitro

Cited by 34 publications

References 31 publications

Inhibition of the serine protease HtrA1 by SerpinE2 suggests an extracellular proteolytic pathway in the control of neural crest migration

Inhibition of the serine protease HtrA1 by SerpinE2 suggests an extracellular proteolytic pathway in the control of neural crest migration

Inhibition of the serine protease HtrA1 by SerpinE2 suggests an extracellular proteolytic pathway in the control of neural crest migration

Urokinase-type plasminogen activator regulates cranial neural crest cell migration in vitro

Contact Info

Product

Resources

About