Limits...
Wnt activity guides facial branchiomotor neuron migration, and involves the PCP pathway and JNK and ROCK kinases.

Vivancos V, Chen P, Spassky N, Qian D, Dabdoub A, Kelley M, Studer M, Guthrie S - Neural Dev (2009)

Bottom Line: We found that Wnt5a is expressed in a caudal high to rostral low gradient in the hindbrain.Inhibition of JNK and ROCK kinases strongly and specifically reduced the FBM migration, as well as blocked the chemoattractant effects of ectopic Wnt proteins.These results provide in vivo evidence that Wnts chemoattract mammalian FBM neurons and that Wnt5a is a candidate to mediate this process.

View Article: PubMed Central - HTML - PubMed

Affiliation: MRC Centre for Developmental Neurobiology, King's College, Guy's Campus, London, SE1 1UL, UK. valerie.vivancos@kcl.ac.uk

ABSTRACT

Background: Wnt proteins play roles in many biological processes, including axon guidance and cell migration. In the mammalian hindbrain, facial branchiomotor (FBM) neurons undergo a striking rostral to caudal migration, yet little is known of the underlying molecular mechanisms. In this study, we investigated a possible role of Wnts and the planar cell polarity (PCP) pathway in this process.

Results: Here we demonstrate a novel role for Wnt proteins in guiding FBM neurons during their rostral to caudal migration in the hindbrain. We found that Wnt5a is expressed in a caudal high to rostral low gradient in the hindbrain. Wnt-coated beads chemoattracted FBM neurons to ectopic positions in an explant migration assay. The rostrocaudal FBM migration was moderately perturbed in Wnt5a mutant embryos and severely disrupted in Frizzled3 mutant mouse embryos, and was aberrant following inhibition of Wnt function by secreted Frizzled-related proteins. We also show the involvement of the Wnt/PCP pathway in mammalian FBM neuron migration. Thus, mutations in two PCP genes, Vangl2 and Scribble, caused severe defects in FBM migration. Inhibition of JNK and ROCK kinases strongly and specifically reduced the FBM migration, as well as blocked the chemoattractant effects of ectopic Wnt proteins.

Conclusion: These results provide in vivo evidence that Wnts chemoattract mammalian FBM neurons and that Wnt5a is a candidate to mediate this process. Molecules of the PCP pathway and the JNK and ROCK kinases also play a role in the FBM migration and are likely mediators of Wnt signalling.

Show MeSH

Related in: MedlinePlus

Spatiotemporal pattern of facial branchiomotor (FBM) neuronal migration in vivo and in explants. (A-C) Schematic representations of mouse embryonic hindbrain at embryonic stages (E)10.5 (A), E11.5 (B) and E12.5 (C). FBM neurons are shown by black dots and migrate from rhombomere (r)4 (E10.5) to r6 (E12.5). Grey patches represent dorsal exit points of motor axons. (D-F) Islet-1 in situ hybridisation on flatmounted hindbrains showing FBM neurons migrating from r4 to r6 at E10.5 (D), E11.5 (E) and E12.5 (F). (G-I) Hindbrain explants cultured on filters and immunostained with anti-Islet 1/2 antibody. Time 0 h (G) represents the beginning of culture period when some FBM neurons have started to migrate into r5. Time 24 h (H) shows that more FBM neurons are present in r5 and that some have started to turn dorsally into r6. Time 48 h (I) shows FBM neurons that have reached their final destination in r6 to form a nucleus. TN, trigeminal motor nucleus. Scale bars: 500 μm in (D-F); 250 μm in (G-I).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2654884&req=5

Figure 1: Spatiotemporal pattern of facial branchiomotor (FBM) neuronal migration in vivo and in explants. (A-C) Schematic representations of mouse embryonic hindbrain at embryonic stages (E)10.5 (A), E11.5 (B) and E12.5 (C). FBM neurons are shown by black dots and migrate from rhombomere (r)4 (E10.5) to r6 (E12.5). Grey patches represent dorsal exit points of motor axons. (D-F) Islet-1 in situ hybridisation on flatmounted hindbrains showing FBM neurons migrating from r4 to r6 at E10.5 (D), E11.5 (E) and E12.5 (F). (G-I) Hindbrain explants cultured on filters and immunostained with anti-Islet 1/2 antibody. Time 0 h (G) represents the beginning of culture period when some FBM neurons have started to migrate into r5. Time 24 h (H) shows that more FBM neurons are present in r5 and that some have started to turn dorsally into r6. Time 48 h (I) shows FBM neurons that have reached their final destination in r6 to form a nucleus. TN, trigeminal motor nucleus. Scale bars: 500 μm in (D-F); 250 μm in (G-I).

Mentions: In the mouse embryo, FBM migration occurs between E10.5 and E14.5. FBM neurons are born in r4 from E9.5 onwards; and start migrating at E10.5, reaching r5 by E11.5 and r6 by E12.5 (Figure 1A–C), [2,4]. In r6, neurons migrate laterally,, starting to form a nucleus by E12.5 (Figure 1C), with nucleus formation continuing until E14.5. The migration can be followed by in situ hybridisation for Islet-1, which is motor neuron-specific at r4-6 axial levels [30] (Figure 1D–F).


Wnt activity guides facial branchiomotor neuron migration, and involves the PCP pathway and JNK and ROCK kinases.

Vivancos V, Chen P, Spassky N, Qian D, Dabdoub A, Kelley M, Studer M, Guthrie S - Neural Dev (2009)

Spatiotemporal pattern of facial branchiomotor (FBM) neuronal migration in vivo and in explants. (A-C) Schematic representations of mouse embryonic hindbrain at embryonic stages (E)10.5 (A), E11.5 (B) and E12.5 (C). FBM neurons are shown by black dots and migrate from rhombomere (r)4 (E10.5) to r6 (E12.5). Grey patches represent dorsal exit points of motor axons. (D-F) Islet-1 in situ hybridisation on flatmounted hindbrains showing FBM neurons migrating from r4 to r6 at E10.5 (D), E11.5 (E) and E12.5 (F). (G-I) Hindbrain explants cultured on filters and immunostained with anti-Islet 1/2 antibody. Time 0 h (G) represents the beginning of culture period when some FBM neurons have started to migrate into r5. Time 24 h (H) shows that more FBM neurons are present in r5 and that some have started to turn dorsally into r6. Time 48 h (I) shows FBM neurons that have reached their final destination in r6 to form a nucleus. TN, trigeminal motor nucleus. Scale bars: 500 μm in (D-F); 250 μm in (G-I).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2654884&req=5

Figure 1: Spatiotemporal pattern of facial branchiomotor (FBM) neuronal migration in vivo and in explants. (A-C) Schematic representations of mouse embryonic hindbrain at embryonic stages (E)10.5 (A), E11.5 (B) and E12.5 (C). FBM neurons are shown by black dots and migrate from rhombomere (r)4 (E10.5) to r6 (E12.5). Grey patches represent dorsal exit points of motor axons. (D-F) Islet-1 in situ hybridisation on flatmounted hindbrains showing FBM neurons migrating from r4 to r6 at E10.5 (D), E11.5 (E) and E12.5 (F). (G-I) Hindbrain explants cultured on filters and immunostained with anti-Islet 1/2 antibody. Time 0 h (G) represents the beginning of culture period when some FBM neurons have started to migrate into r5. Time 24 h (H) shows that more FBM neurons are present in r5 and that some have started to turn dorsally into r6. Time 48 h (I) shows FBM neurons that have reached their final destination in r6 to form a nucleus. TN, trigeminal motor nucleus. Scale bars: 500 μm in (D-F); 250 μm in (G-I).
Mentions: In the mouse embryo, FBM migration occurs between E10.5 and E14.5. FBM neurons are born in r4 from E9.5 onwards; and start migrating at E10.5, reaching r5 by E11.5 and r6 by E12.5 (Figure 1A–C), [2,4]. In r6, neurons migrate laterally,, starting to form a nucleus by E12.5 (Figure 1C), with nucleus formation continuing until E14.5. The migration can be followed by in situ hybridisation for Islet-1, which is motor neuron-specific at r4-6 axial levels [30] (Figure 1D–F).

Bottom Line: We found that Wnt5a is expressed in a caudal high to rostral low gradient in the hindbrain.Inhibition of JNK and ROCK kinases strongly and specifically reduced the FBM migration, as well as blocked the chemoattractant effects of ectopic Wnt proteins.These results provide in vivo evidence that Wnts chemoattract mammalian FBM neurons and that Wnt5a is a candidate to mediate this process.

View Article: PubMed Central - HTML - PubMed

Affiliation: MRC Centre for Developmental Neurobiology, King's College, Guy's Campus, London, SE1 1UL, UK. valerie.vivancos@kcl.ac.uk

ABSTRACT

Background: Wnt proteins play roles in many biological processes, including axon guidance and cell migration. In the mammalian hindbrain, facial branchiomotor (FBM) neurons undergo a striking rostral to caudal migration, yet little is known of the underlying molecular mechanisms. In this study, we investigated a possible role of Wnts and the planar cell polarity (PCP) pathway in this process.

Results: Here we demonstrate a novel role for Wnt proteins in guiding FBM neurons during their rostral to caudal migration in the hindbrain. We found that Wnt5a is expressed in a caudal high to rostral low gradient in the hindbrain. Wnt-coated beads chemoattracted FBM neurons to ectopic positions in an explant migration assay. The rostrocaudal FBM migration was moderately perturbed in Wnt5a mutant embryos and severely disrupted in Frizzled3 mutant mouse embryos, and was aberrant following inhibition of Wnt function by secreted Frizzled-related proteins. We also show the involvement of the Wnt/PCP pathway in mammalian FBM neuron migration. Thus, mutations in two PCP genes, Vangl2 and Scribble, caused severe defects in FBM migration. Inhibition of JNK and ROCK kinases strongly and specifically reduced the FBM migration, as well as blocked the chemoattractant effects of ectopic Wnt proteins.

Conclusion: These results provide in vivo evidence that Wnts chemoattract mammalian FBM neurons and that Wnt5a is a candidate to mediate this process. Molecules of the PCP pathway and the JNK and ROCK kinases also play a role in the FBM migration and are likely mediators of Wnt signalling.

Show MeSH
Related in: MedlinePlus