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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.


Related in: MedlinePlus

Hs2st is expressed near FBM neurons and is essential for their appropriate migration. (A) Whole-mount X-gal staining of 10.5 dpc Hs2stLacz/+ hindbrains (n=5) shows Hs2st expression in r4 (arrow) adjacent to the motor column, visualised by Isl1 ISH (arrowhead). (B) Transverse 10.5 dpc Hs2stLacz/+ sections through r4 level were X-gal stained and then immunostained for ISL1 to demonstrate Hs2st expression adjacent to FBM neurons (VIIm; the X-gal stain was pseudocoloured red in the right-hand panel). The arrow indicates Hs2st expression. (C) Whole-mount X-gal staining of 12.5 dpc Hs2stLacz/+ hindbrains (n=3) shows Hs2st expression in the midline area (red wavy arrow). (D) Isl1 whole-mount ISH of Hs2stLacz/Lacz and wild-type hindbrains (n=6 each); brackets indicate the width of the FBM neuron stream. (E) Lateral views of 11.5 dpc Hs2stLacz/Lacz heads and controls, immunolabelled for TUJ1 (n=3 each). The Vmd, Vmx and Vop nerves extend from the trigeminal ganglion (Vg), and the VIIct, VIIbm and VIIgspn nerves from the facial ganglion (VIIg) in both genotypes. Scale bars: 200 μm in A,C,E; 400 μm in D; 50 μm in B.
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DEV126854F2: Hs2st is expressed near FBM neurons and is essential for their appropriate migration. (A) Whole-mount X-gal staining of 10.5 dpc Hs2stLacz/+ hindbrains (n=5) shows Hs2st expression in r4 (arrow) adjacent to the motor column, visualised by Isl1 ISH (arrowhead). (B) Transverse 10.5 dpc Hs2stLacz/+ sections through r4 level were X-gal stained and then immunostained for ISL1 to demonstrate Hs2st expression adjacent to FBM neurons (VIIm; the X-gal stain was pseudocoloured red in the right-hand panel). The arrow indicates Hs2st expression. (C) Whole-mount X-gal staining of 12.5 dpc Hs2stLacz/+ hindbrains (n=3) shows Hs2st expression in the midline area (red wavy arrow). (D) Isl1 whole-mount ISH of Hs2stLacz/Lacz and wild-type hindbrains (n=6 each); brackets indicate the width of the FBM neuron stream. (E) Lateral views of 11.5 dpc Hs2stLacz/Lacz heads and controls, immunolabelled for TUJ1 (n=3 each). The Vmd, Vmx and Vop nerves extend from the trigeminal ganglion (Vg), and the VIIct, VIIbm and VIIgspn nerves from the facial ganglion (VIIg) in both genotypes. Scale bars: 200 μm in A,C,E; 400 μm in D; 50 μm in B.

Mentions: To determine the expression pattern of HS2ST during hindbrain development, we used mice carrying an Hs2stLacz knock-in allele that recapitulates endogenous Hs2st expression when visualised as β-galactosidase-mediated X-gal staining (Bullock et al., 1998). Hs2stLacz/+ hindbrains at 10.5 dpc showed prominent staining in r4, close to the domain in which FBM neurons differentiate (Fig. 2A). The Hs2st expression domain was adjacent to, but did not overlap with, the area that contains FBM neurons (Fig. 2B). By 12.5 dpc, Hs2st expression seemed to be restricted to the midline region (Fig. 2C). These expression patterns raise the possibility that HS2ST modifies proteoglycans that regulate FBM neuron development in trans. To determine whether HS2ST is required for FBM neuron migration, we examined Hs2st- (Hs2stLacz/Lacz) hindbrains by Isl1 ISH. We observed splitting of the migratory stream in all mutants examined (Fig. 2D). By contrast, whole-mount TUJ1 immunolabelling showed normal axon extension of all facial and trigeminal nerve branches in mutants (Fig. 2E). These results suggest that 2-O-sulfotransferase is important for FBM neuron migration, but not cranial axon guidance.Fig. 2.


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)

Hs2st is expressed near FBM neurons and is essential for their appropriate migration. (A) Whole-mount X-gal staining of 10.5 dpc Hs2stLacz/+ hindbrains (n=5) shows Hs2st expression in r4 (arrow) adjacent to the motor column, visualised by Isl1 ISH (arrowhead). (B) Transverse 10.5 dpc Hs2stLacz/+ sections through r4 level were X-gal stained and then immunostained for ISL1 to demonstrate Hs2st expression adjacent to FBM neurons (VIIm; the X-gal stain was pseudocoloured red in the right-hand panel). The arrow indicates Hs2st expression. (C) Whole-mount X-gal staining of 12.5 dpc Hs2stLacz/+ hindbrains (n=3) shows Hs2st expression in the midline area (red wavy arrow). (D) Isl1 whole-mount ISH of Hs2stLacz/Lacz and wild-type hindbrains (n=6 each); brackets indicate the width of the FBM neuron stream. (E) Lateral views of 11.5 dpc Hs2stLacz/Lacz heads and controls, immunolabelled for TUJ1 (n=3 each). The Vmd, Vmx and Vop nerves extend from the trigeminal ganglion (Vg), and the VIIct, VIIbm and VIIgspn nerves from the facial ganglion (VIIg) in both genotypes. Scale bars: 200 μm in A,C,E; 400 μm in D; 50 μm in B.
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DEV126854F2: Hs2st is expressed near FBM neurons and is essential for their appropriate migration. (A) Whole-mount X-gal staining of 10.5 dpc Hs2stLacz/+ hindbrains (n=5) shows Hs2st expression in r4 (arrow) adjacent to the motor column, visualised by Isl1 ISH (arrowhead). (B) Transverse 10.5 dpc Hs2stLacz/+ sections through r4 level were X-gal stained and then immunostained for ISL1 to demonstrate Hs2st expression adjacent to FBM neurons (VIIm; the X-gal stain was pseudocoloured red in the right-hand panel). The arrow indicates Hs2st expression. (C) Whole-mount X-gal staining of 12.5 dpc Hs2stLacz/+ hindbrains (n=3) shows Hs2st expression in the midline area (red wavy arrow). (D) Isl1 whole-mount ISH of Hs2stLacz/Lacz and wild-type hindbrains (n=6 each); brackets indicate the width of the FBM neuron stream. (E) Lateral views of 11.5 dpc Hs2stLacz/Lacz heads and controls, immunolabelled for TUJ1 (n=3 each). The Vmd, Vmx and Vop nerves extend from the trigeminal ganglion (Vg), and the VIIct, VIIbm and VIIgspn nerves from the facial ganglion (VIIg) in both genotypes. Scale bars: 200 μm in A,C,E; 400 μm in D; 50 μm in B.
Mentions: To determine the expression pattern of HS2ST during hindbrain development, we used mice carrying an Hs2stLacz knock-in allele that recapitulates endogenous Hs2st expression when visualised as β-galactosidase-mediated X-gal staining (Bullock et al., 1998). Hs2stLacz/+ hindbrains at 10.5 dpc showed prominent staining in r4, close to the domain in which FBM neurons differentiate (Fig. 2A). The Hs2st expression domain was adjacent to, but did not overlap with, the area that contains FBM neurons (Fig. 2B). By 12.5 dpc, Hs2st expression seemed to be restricted to the midline region (Fig. 2C). These expression patterns raise the possibility that HS2ST modifies proteoglycans that regulate FBM neuron development in trans. To determine whether HS2ST is required for FBM neuron migration, we examined Hs2st- (Hs2stLacz/Lacz) hindbrains by Isl1 ISH. We observed splitting of the migratory stream in all mutants examined (Fig. 2D). By contrast, whole-mount TUJ1 immunolabelling showed normal axon extension of all facial and trigeminal nerve branches in mutants (Fig. 2E). These results suggest that 2-O-sulfotransferase is important for FBM neuron migration, but not cranial axon guidance.Fig. 2.

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.


Related in: MedlinePlus