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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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Summary of results and a model of retinoic acid signalling at the rhombic lip. A. Schematic summary of in situ hybridisation expression domains showing: Cath1 (pink) at the rhombic lip; retinoic acid (RA) synthesis (green: Raldh2 &Cyp1B1) in the roof plate and in the meninges; retinoic acid catabolism (orange: Cyp26A1, Cyp26B1, and Cyp26C1) in the ventricular zone and in the roof plate; retinoic acid binding (blue: Crabp1) in the mantle layer. B. Cellular events illustrated against the same template as in A, where proliferative cells (grey) and migrating rhombic lip derivatives (black) are shown relative to the production of RA (green) C. Model of retinoic acid accumulation resulting from interplay and spatial distribution of retinoic acid signalling components within the dorsal neuroepithelium (left), rhombic lip (middle) and roof plate (right). Expression patterns predict a high concentration of retinoic acid at the rhombic lip. Crabp1 could either play a role in buffering RA or in facilitating its transport to the nucleus as cells exit division. Receptor expression (RAR and RXR) is uniform across the rhombic lip and therefore unlikely to confer signalling specificity.
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Figure 10: Summary of results and a model of retinoic acid signalling at the rhombic lip. A. Schematic summary of in situ hybridisation expression domains showing: Cath1 (pink) at the rhombic lip; retinoic acid (RA) synthesis (green: Raldh2 &Cyp1B1) in the roof plate and in the meninges; retinoic acid catabolism (orange: Cyp26A1, Cyp26B1, and Cyp26C1) in the ventricular zone and in the roof plate; retinoic acid binding (blue: Crabp1) in the mantle layer. B. Cellular events illustrated against the same template as in A, where proliferative cells (grey) and migrating rhombic lip derivatives (black) are shown relative to the production of RA (green) C. Model of retinoic acid accumulation resulting from interplay and spatial distribution of retinoic acid signalling components within the dorsal neuroepithelium (left), rhombic lip (middle) and roof plate (right). Expression patterns predict a high concentration of retinoic acid at the rhombic lip. Crabp1 could either play a role in buffering RA or in facilitating its transport to the nucleus as cells exit division. Receptor expression (RAR and RXR) is uniform across the rhombic lip and therefore unlikely to confer signalling specificity.

Mentions: We have used in situ hybridisation to examine the expression domains of retinoic acid signalling components during late avian hindbrain development. We show that retinoic acid synthesis, catabolism, binding and receptor distribution occur in defined temporal and spatial territories. These observations support a role in the development of specific neuronal populations for retinoic acid signalling that is distinct from its earlier function in patterning the rostrocaudal axis. In contrast to earlier developmental stages, synthetic and catabolic enzymes are co-localised in the same cell groups (Table 1) indicating a highly localised usage of retinoic acid. In particular, detailed characterisation of signalling components at the rhombic lip suggests a role for local retinoic acid signalling at the interface between roofplate and neural tube (Figure 10).


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)

Summary of results and a model of retinoic acid signalling at the rhombic lip. A. Schematic summary of in situ hybridisation expression domains showing: Cath1 (pink) at the rhombic lip; retinoic acid (RA) synthesis (green: Raldh2 &Cyp1B1) in the roof plate and in the meninges; retinoic acid catabolism (orange: Cyp26A1, Cyp26B1, and Cyp26C1) in the ventricular zone and in the roof plate; retinoic acid binding (blue: Crabp1) in the mantle layer. B. Cellular events illustrated against the same template as in A, where proliferative cells (grey) and migrating rhombic lip derivatives (black) are shown relative to the production of RA (green) C. Model of retinoic acid accumulation resulting from interplay and spatial distribution of retinoic acid signalling components within the dorsal neuroepithelium (left), rhombic lip (middle) and roof plate (right). Expression patterns predict a high concentration of retinoic acid at the rhombic lip. Crabp1 could either play a role in buffering RA or in facilitating its transport to the nucleus as cells exit division. Receptor expression (RAR and RXR) is uniform across the rhombic lip and therefore unlikely to confer signalling specificity.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2266733&req=5

Figure 10: Summary of results and a model of retinoic acid signalling at the rhombic lip. A. Schematic summary of in situ hybridisation expression domains showing: Cath1 (pink) at the rhombic lip; retinoic acid (RA) synthesis (green: Raldh2 &Cyp1B1) in the roof plate and in the meninges; retinoic acid catabolism (orange: Cyp26A1, Cyp26B1, and Cyp26C1) in the ventricular zone and in the roof plate; retinoic acid binding (blue: Crabp1) in the mantle layer. B. Cellular events illustrated against the same template as in A, where proliferative cells (grey) and migrating rhombic lip derivatives (black) are shown relative to the production of RA (green) C. Model of retinoic acid accumulation resulting from interplay and spatial distribution of retinoic acid signalling components within the dorsal neuroepithelium (left), rhombic lip (middle) and roof plate (right). Expression patterns predict a high concentration of retinoic acid at the rhombic lip. Crabp1 could either play a role in buffering RA or in facilitating its transport to the nucleus as cells exit division. Receptor expression (RAR and RXR) is uniform across the rhombic lip and therefore unlikely to confer signalling specificity.
Mentions: We have used in situ hybridisation to examine the expression domains of retinoic acid signalling components during late avian hindbrain development. We show that retinoic acid synthesis, catabolism, binding and receptor distribution occur in defined temporal and spatial territories. These observations support a role in the development of specific neuronal populations for retinoic acid signalling that is distinct from its earlier function in patterning the rostrocaudal axis. In contrast to earlier developmental stages, synthetic and catabolic enzymes are co-localised in the same cell groups (Table 1) indicating a highly localised usage of retinoic acid. In particular, detailed characterisation of signalling components at the rhombic lip suggests a role for local retinoic acid signalling at the interface between roofplate and neural tube (Figure 10).

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