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2- and 6-O-sulfated proteoglycans have distinct and complementary roles in cranial axon guidance and motor neuron migration.

Tillo M, Charoy C, Schwarz Q, Maden CH, Davidson K, Fantin A, Ruhrberg C - Development (2016)

Bottom Line: The correct migration and axon extension of neurons in the developing nervous system is essential for the appropriate wiring and function of neural networks.We show that the 6-O-sulfotransferases HS6ST1 and HS6ST2 are essential for cranial axon patterning, whilst the 2-O-sulfotransferase HS2ST (also known as HS2ST1) is important to regulate the migration of facial branchiomotor (FBM) neurons in the hindbrain.We have also investigated how HS2ST interacts with other signals in the hindbrain and show that fibroblast growth factor (FGF) signalling regulates FBM neuron migration in an HS2ST-dependent manner.

View Article: PubMed Central - PubMed

Affiliation: UCL Institute of Ophthalmology, University College London, 11-43 Bath Street, London EC1V 9EL, UK.

No MeSH data available.


VEGF does not require HS2ST to control FBM neuron migration. (A) Transverse sections through 12.5 dpc r6, immunolabelled for ISL1, TUJ1 and the vascular marker IB4; arrows indicate similar stream splitting of FBM neurons in Hs2stLacz/Lacz, Nrp1−/− and Vegfa120/120 mice (n=3 each). (B) Hindbrain explants containing VEGF165 beads (position indicated with red circles) were immunostained for ISL1; red arrows indicate the leading edge of FBM neurons migrating towards the beads. The distance migrated on the implanted relative to the control side of each hindbrain is shown as mean±s.e.m. Hs2st+/+, n=15; Hs2stLacz/Lacz, n=7. *P<0.05, **P<0.01, paired t-test. Scale bars: 200 μm.
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DEV126854F3: VEGF does not require HS2ST to control FBM neuron migration. (A) Transverse sections through 12.5 dpc r6, immunolabelled for ISL1, TUJ1 and the vascular marker IB4; arrows indicate similar stream splitting of FBM neurons in Hs2stLacz/Lacz, Nrp1−/− and Vegfa120/120 mice (n=3 each). (B) Hindbrain explants containing VEGF165 beads (position indicated with red circles) were immunostained for ISL1; red arrows indicate the leading edge of FBM neurons migrating towards the beads. The distance migrated on the implanted relative to the control side of each hindbrain is shown as mean±s.e.m. Hs2st+/+, n=15; Hs2stLacz/Lacz, n=7. *P<0.05, **P<0.01, paired t-test. Scale bars: 200 μm.

Mentions: HSPGs interact with VEGF and its receptor NRP1 (Sarrazin et al., 2011). We therefore asked if loss of 2-O-sulfated HSPGs caused an FBM neuron defect similar to that caused by loss of VEGF signalling through NRP1 (Schwarz et al., 2004). Comparable to Nrp1- mice and Vegfa120/120 mice lacking NRP1-binding VEGF (Schwarz et al., 2004), migrating FBM neurons split into two main streams in Hs2st- hindbrains (Fig. 3A). To examine whether HS2ST-modified HSPGs were required for VEGF-induced FBM neuron migration, we implanted VEGF165-coated heparin beads into Hs2st- and littermate control hindbrain explants. As previously shown (Schwarz et al., 2004), FBM neurons migrated towards the beads in controls (Fig. 3B). Unexpectedly, these neurons also migrated towards the beads in Hs2st- hindbrains (Fig. 3B). Quantification confirmed that VEGF165 beads promoted FBM neuron migration in both genotypes (Fig. 3B). Despite the similar in vivo phenotypes of Hs2st- and Vegfa120/120 mice, HS2ST-modified HSPGs are therefore not required for VEGF-induced FBM neuron migration.Fig. 3.


2- and 6-O-sulfated proteoglycans have distinct and complementary roles in cranial axon guidance and motor neuron migration.

Tillo M, Charoy C, Schwarz Q, Maden CH, Davidson K, Fantin A, Ruhrberg C - Development (2016)

VEGF does not require HS2ST to control FBM neuron migration. (A) Transverse sections through 12.5 dpc r6, immunolabelled for ISL1, TUJ1 and the vascular marker IB4; arrows indicate similar stream splitting of FBM neurons in Hs2stLacz/Lacz, Nrp1−/− and Vegfa120/120 mice (n=3 each). (B) Hindbrain explants containing VEGF165 beads (position indicated with red circles) were immunostained for ISL1; red arrows indicate the leading edge of FBM neurons migrating towards the beads. The distance migrated on the implanted relative to the control side of each hindbrain is shown as mean±s.e.m. Hs2st+/+, n=15; Hs2stLacz/Lacz, n=7. *P<0.05, **P<0.01, paired t-test. Scale bars: 200 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4920156&req=5

DEV126854F3: VEGF does not require HS2ST to control FBM neuron migration. (A) Transverse sections through 12.5 dpc r6, immunolabelled for ISL1, TUJ1 and the vascular marker IB4; arrows indicate similar stream splitting of FBM neurons in Hs2stLacz/Lacz, Nrp1−/− and Vegfa120/120 mice (n=3 each). (B) Hindbrain explants containing VEGF165 beads (position indicated with red circles) were immunostained for ISL1; red arrows indicate the leading edge of FBM neurons migrating towards the beads. The distance migrated on the implanted relative to the control side of each hindbrain is shown as mean±s.e.m. Hs2st+/+, n=15; Hs2stLacz/Lacz, n=7. *P<0.05, **P<0.01, paired t-test. Scale bars: 200 μm.
Mentions: HSPGs interact with VEGF and its receptor NRP1 (Sarrazin et al., 2011). We therefore asked if loss of 2-O-sulfated HSPGs caused an FBM neuron defect similar to that caused by loss of VEGF signalling through NRP1 (Schwarz et al., 2004). Comparable to Nrp1- mice and Vegfa120/120 mice lacking NRP1-binding VEGF (Schwarz et al., 2004), migrating FBM neurons split into two main streams in Hs2st- hindbrains (Fig. 3A). To examine whether HS2ST-modified HSPGs were required for VEGF-induced FBM neuron migration, we implanted VEGF165-coated heparin beads into Hs2st- and littermate control hindbrain explants. As previously shown (Schwarz et al., 2004), FBM neurons migrated towards the beads in controls (Fig. 3B). Unexpectedly, these neurons also migrated towards the beads in Hs2st- hindbrains (Fig. 3B). Quantification confirmed that VEGF165 beads promoted FBM neuron migration in both genotypes (Fig. 3B). Despite the similar in vivo phenotypes of Hs2st- and Vegfa120/120 mice, HS2ST-modified HSPGs are therefore not required for VEGF-induced FBM neuron migration.Fig. 3.

Bottom Line: The correct migration and axon extension of neurons in the developing nervous system is essential for the appropriate wiring and function of neural networks.We show that the 6-O-sulfotransferases HS6ST1 and HS6ST2 are essential for cranial axon patterning, whilst the 2-O-sulfotransferase HS2ST (also known as HS2ST1) is important to regulate the migration of facial branchiomotor (FBM) neurons in the hindbrain.We have also investigated how HS2ST interacts with other signals in the hindbrain and show that fibroblast growth factor (FGF) signalling regulates FBM neuron migration in an HS2ST-dependent manner.

View Article: PubMed Central - PubMed

Affiliation: UCL Institute of Ophthalmology, University College London, 11-43 Bath Street, London EC1V 9EL, UK.

No MeSH data available.