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Retinoic acid is a potential dorsalising signal in the late embryonic chick hindbrain.

Wilson LJ, Myat A, Sharma A, Maden M, Wingate RJ - BMC Dev. Biol. (2007)

Bottom Line: Intriguingly, transcripts of cellular retinoic acid binding protein 1 are always found at the interface between dividing and post-mitotic cells.At the rhombic lip, retinoic acid is likely to act as a dorsalising factor in parallel with other roofplate signalling pathways.While its precise role is unclear, retinoic acid is potentially well placed to regulate temporally determined cell fate decisions within the rhombic lip precursor pool.

View Article: PubMed Central - HTML - PubMed

Affiliation: MRC Centre for Developmental Neurobiology, King's College London, 4th floor New Hunt's House, Guy's Campus, London SE1 1UL, UK. leigh.wilson@kcl.ac.uk

ABSTRACT

Background: Human retinoic acid teratogenesis results in malformations of dorsally derived hindbrain structures such as the cerebellum, noradrenergic hindbrain neurons and the precerebellar system. These structures originate from the rhombic lip and adjacent dorsal precursor pools that border the fourth ventricle roofplate. While retinoic acid synthesis is known to occur in the meninges that blanket the hindbrain, the particular sensitivity of only dorsal structures to disruptions in retinoid signalling is puzzling. We therefore looked for evidence within the neural tube for more spatiotemporally specific signalling pathways using an in situ hybridisation screen of known retinoic acid pathway transcripts.

Results: We find that there are highly restricted domains of retinoic acid synthesis and breakdown within specific hindbrain nuclei as well as the ventricular layer and roofplate. Intriguingly, transcripts of cellular retinoic acid binding protein 1 are always found at the interface between dividing and post-mitotic cells. By contrast to earlier stages of development, domains of synthesis and breakdown in post-mitotic neurons are co-localised. At the rhombic lip, expression of the mRNA for retinoic acid synthesising and catabolising enzymes is spatially highly organised with respect to the Cath1-positive precursors of migratory precerebellar neurons.

Conclusion: The late developing hindbrain shows patterns of retinoic acid synthesis and use that are distinct from the well characterised phase of rostrocaudal patterning. Selected post-mitotic populations, such as the locus coeruleus, appear to both make and break down retinoic acid suggesting that a requirement for an autocrine, or at least a highly localised paracrine signalling network, might explain its acute sensitivity to retinoic acid disruption. At the rhombic lip, retinoic acid is likely to act as a dorsalising factor in parallel with other roofplate signalling pathways. While its precise role is unclear, retinoic acid is potentially well placed to regulate temporally determined cell fate decisions within the rhombic lip precursor pool.

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Retinoid signalling at the rhombic lip. Transverse sections taken through the caudal hindbrain at e5 with the roof plate orientated to the right and the dorsal neuroepithelium to the left. A. Cath1 expression at the rhombic lip. B. Cath1 (red) and Gdf7 (in blue) show a non-overlapping interface (arrow). C. Cyp1B1 expression in dorsal neural tube shows a similar expression to Gdf7. D. Cath1 (red) and Cyp1B1 (blue) show no overlap of expression. Cyp1B1 is expressed within the developing blood vessels at the base of the ventricular layer (arrow). E. Cyp26A1 is expressed within the roof plate with highest expression close to the rhombic lip. F. Cath1 (red) and Cyp26A1 (blue) are non-overlapping at their interface (arrow). G. Cyp26C1 is expressed more uniformly throughout the roofplate than Cyp26A1 (E). H. Cath1 (red) and Cyp26C1 (blue) expression is non-overlapping (arrow). I. Cyp26B1 expression is excluded from the rhombic lip J. Cath1 (red) and Cyp26B1 (blue) show complementary expression domains at the ventricular layer boundary of the rhombic lip. K. At the level of the VIIth nerve exit point, Crabp1 is expressed at the interface between ventricular zone and mantle layer. L. Cath1 (red) expression partially overlaps that of Crabp1 (blue) at the interface of the ventricular zone (arrow). Transient spots of Cath1 expression at the exit point of the VIIth nerve are visible at this level (asterisk). Intriguingly, this post-mitotic expression of Cath1 corresponds with a distinct gap in Crabp1 at the overlying ventricular layer boundary. M. At a slightly more rostral level, Crabp1 expression is continuous beneath the ventricular layer. At all levels, there is an extended tail of expression into the mantle layer at the rhombic lip. N. Confocal micrograph of BrdU localisation in s-phase nuclei (arrow).
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Figure 9: Retinoid signalling at the rhombic lip. Transverse sections taken through the caudal hindbrain at e5 with the roof plate orientated to the right and the dorsal neuroepithelium to the left. A. Cath1 expression at the rhombic lip. B. Cath1 (red) and Gdf7 (in blue) show a non-overlapping interface (arrow). C. Cyp1B1 expression in dorsal neural tube shows a similar expression to Gdf7. D. Cath1 (red) and Cyp1B1 (blue) show no overlap of expression. Cyp1B1 is expressed within the developing blood vessels at the base of the ventricular layer (arrow). E. Cyp26A1 is expressed within the roof plate with highest expression close to the rhombic lip. F. Cath1 (red) and Cyp26A1 (blue) are non-overlapping at their interface (arrow). G. Cyp26C1 is expressed more uniformly throughout the roofplate than Cyp26A1 (E). H. Cath1 (red) and Cyp26C1 (blue) expression is non-overlapping (arrow). I. Cyp26B1 expression is excluded from the rhombic lip J. Cath1 (red) and Cyp26B1 (blue) show complementary expression domains at the ventricular layer boundary of the rhombic lip. K. At the level of the VIIth nerve exit point, Crabp1 is expressed at the interface between ventricular zone and mantle layer. L. Cath1 (red) expression partially overlaps that of Crabp1 (blue) at the interface of the ventricular zone (arrow). Transient spots of Cath1 expression at the exit point of the VIIth nerve are visible at this level (asterisk). Intriguingly, this post-mitotic expression of Cath1 corresponds with a distinct gap in Crabp1 at the overlying ventricular layer boundary. M. At a slightly more rostral level, Crabp1 expression is continuous beneath the ventricular layer. At all levels, there is an extended tail of expression into the mantle layer at the rhombic lip. N. Confocal micrograph of BrdU localisation in s-phase nuclei (arrow).

Mentions: This survey of gene expression indicates a complex pattern of retinoic acid synthesis, transduction and breakdown. Amongst various emergent themes, the spatial domains of transcripts at the roofplate and the rhombic lip suggest that expression boundaries at this interface are tightly regulated. We examined distribution of gene expression of Cyp genes and Crabp1 at a single time-point (e5) using the basic helix-loop-helix transcription factor, Atonal1 (Cath1), as a marker of definitive rhombic lip derivatives (Fig. 9A[18,19]) and Gdf7 as a marker of the boundary of the non-neuronal roofplate (Fig. 9B[48,49]).


Retinoic acid is a potential dorsalising signal in the late embryonic chick hindbrain.

Wilson LJ, Myat A, Sharma A, Maden M, Wingate RJ - BMC Dev. Biol. (2007)

Retinoid signalling at the rhombic lip. Transverse sections taken through the caudal hindbrain at e5 with the roof plate orientated to the right and the dorsal neuroepithelium to the left. A. Cath1 expression at the rhombic lip. B. Cath1 (red) and Gdf7 (in blue) show a non-overlapping interface (arrow). C. Cyp1B1 expression in dorsal neural tube shows a similar expression to Gdf7. D. Cath1 (red) and Cyp1B1 (blue) show no overlap of expression. Cyp1B1 is expressed within the developing blood vessels at the base of the ventricular layer (arrow). E. Cyp26A1 is expressed within the roof plate with highest expression close to the rhombic lip. F. Cath1 (red) and Cyp26A1 (blue) are non-overlapping at their interface (arrow). G. Cyp26C1 is expressed more uniformly throughout the roofplate than Cyp26A1 (E). H. Cath1 (red) and Cyp26C1 (blue) expression is non-overlapping (arrow). I. Cyp26B1 expression is excluded from the rhombic lip J. Cath1 (red) and Cyp26B1 (blue) show complementary expression domains at the ventricular layer boundary of the rhombic lip. K. At the level of the VIIth nerve exit point, Crabp1 is expressed at the interface between ventricular zone and mantle layer. L. Cath1 (red) expression partially overlaps that of Crabp1 (blue) at the interface of the ventricular zone (arrow). Transient spots of Cath1 expression at the exit point of the VIIth nerve are visible at this level (asterisk). Intriguingly, this post-mitotic expression of Cath1 corresponds with a distinct gap in Crabp1 at the overlying ventricular layer boundary. M. At a slightly more rostral level, Crabp1 expression is continuous beneath the ventricular layer. At all levels, there is an extended tail of expression into the mantle layer at the rhombic lip. N. Confocal micrograph of BrdU localisation in s-phase nuclei (arrow).
© Copyright Policy - open-access
Related In: Results  -  Collection

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Figure 9: Retinoid signalling at the rhombic lip. Transverse sections taken through the caudal hindbrain at e5 with the roof plate orientated to the right and the dorsal neuroepithelium to the left. A. Cath1 expression at the rhombic lip. B. Cath1 (red) and Gdf7 (in blue) show a non-overlapping interface (arrow). C. Cyp1B1 expression in dorsal neural tube shows a similar expression to Gdf7. D. Cath1 (red) and Cyp1B1 (blue) show no overlap of expression. Cyp1B1 is expressed within the developing blood vessels at the base of the ventricular layer (arrow). E. Cyp26A1 is expressed within the roof plate with highest expression close to the rhombic lip. F. Cath1 (red) and Cyp26A1 (blue) are non-overlapping at their interface (arrow). G. Cyp26C1 is expressed more uniformly throughout the roofplate than Cyp26A1 (E). H. Cath1 (red) and Cyp26C1 (blue) expression is non-overlapping (arrow). I. Cyp26B1 expression is excluded from the rhombic lip J. Cath1 (red) and Cyp26B1 (blue) show complementary expression domains at the ventricular layer boundary of the rhombic lip. K. At the level of the VIIth nerve exit point, Crabp1 is expressed at the interface between ventricular zone and mantle layer. L. Cath1 (red) expression partially overlaps that of Crabp1 (blue) at the interface of the ventricular zone (arrow). Transient spots of Cath1 expression at the exit point of the VIIth nerve are visible at this level (asterisk). Intriguingly, this post-mitotic expression of Cath1 corresponds with a distinct gap in Crabp1 at the overlying ventricular layer boundary. M. At a slightly more rostral level, Crabp1 expression is continuous beneath the ventricular layer. At all levels, there is an extended tail of expression into the mantle layer at the rhombic lip. N. Confocal micrograph of BrdU localisation in s-phase nuclei (arrow).
Mentions: This survey of gene expression indicates a complex pattern of retinoic acid synthesis, transduction and breakdown. Amongst various emergent themes, the spatial domains of transcripts at the roofplate and the rhombic lip suggest that expression boundaries at this interface are tightly regulated. We examined distribution of gene expression of Cyp genes and Crabp1 at a single time-point (e5) using the basic helix-loop-helix transcription factor, Atonal1 (Cath1), as a marker of definitive rhombic lip derivatives (Fig. 9A[18,19]) and Gdf7 as a marker of the boundary of the non-neuronal roofplate (Fig. 9B[48,49]).

Bottom Line: Intriguingly, transcripts of cellular retinoic acid binding protein 1 are always found at the interface between dividing and post-mitotic cells.At the rhombic lip, retinoic acid is likely to act as a dorsalising factor in parallel with other roofplate signalling pathways.While its precise role is unclear, retinoic acid is potentially well placed to regulate temporally determined cell fate decisions within the rhombic lip precursor pool.

View Article: PubMed Central - HTML - PubMed

Affiliation: MRC Centre for Developmental Neurobiology, King's College London, 4th floor New Hunt's House, Guy's Campus, London SE1 1UL, UK. leigh.wilson@kcl.ac.uk

ABSTRACT

Background: Human retinoic acid teratogenesis results in malformations of dorsally derived hindbrain structures such as the cerebellum, noradrenergic hindbrain neurons and the precerebellar system. These structures originate from the rhombic lip and adjacent dorsal precursor pools that border the fourth ventricle roofplate. While retinoic acid synthesis is known to occur in the meninges that blanket the hindbrain, the particular sensitivity of only dorsal structures to disruptions in retinoid signalling is puzzling. We therefore looked for evidence within the neural tube for more spatiotemporally specific signalling pathways using an in situ hybridisation screen of known retinoic acid pathway transcripts.

Results: We find that there are highly restricted domains of retinoic acid synthesis and breakdown within specific hindbrain nuclei as well as the ventricular layer and roofplate. Intriguingly, transcripts of cellular retinoic acid binding protein 1 are always found at the interface between dividing and post-mitotic cells. By contrast to earlier stages of development, domains of synthesis and breakdown in post-mitotic neurons are co-localised. At the rhombic lip, expression of the mRNA for retinoic acid synthesising and catabolising enzymes is spatially highly organised with respect to the Cath1-positive precursors of migratory precerebellar neurons.

Conclusion: The late developing hindbrain shows patterns of retinoic acid synthesis and use that are distinct from the well characterised phase of rostrocaudal patterning. Selected post-mitotic populations, such as the locus coeruleus, appear to both make and break down retinoic acid suggesting that a requirement for an autocrine, or at least a highly localised paracrine signalling network, might explain its acute sensitivity to retinoic acid disruption. At the rhombic lip, retinoic acid is likely to act as a dorsalising factor in parallel with other roofplate signalling pathways. While its precise role is unclear, retinoic acid is potentially well placed to regulate temporally determined cell fate decisions within the rhombic lip precursor pool.

Show MeSH
Related in: MedlinePlus