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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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Expression of Cyp1B1. A. Cyp1B1 expression at e5 is located in the developing meninges (*). B. Transverse section through the cerebellar region (black dashed line in A) shows expression in the blood vessels within the neural tube (arrow) and the cranial mesenchyme (*). C. Transverse section through the rostral hindbrain (white dashed line in A) reveals expression at the rhombic lip (inset at higher magnification).D. Meningeal membrane expression at e7.5 (*). E. Transverse section through cerebellum at e7.5 (black dashed line in D) shows meningeal, vascular expression. F. Transverse section through e7.5 rostral hindbrain (white dashed line in D) showing expression in the meninges (*) and blood vessels.
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Figure 4: Expression of Cyp1B1. A. Cyp1B1 expression at e5 is located in the developing meninges (*). B. Transverse section through the cerebellar region (black dashed line in A) shows expression in the blood vessels within the neural tube (arrow) and the cranial mesenchyme (*). C. Transverse section through the rostral hindbrain (white dashed line in A) reveals expression at the rhombic lip (inset at higher magnification).D. Meningeal membrane expression at e7.5 (*). E. Transverse section through cerebellum at e7.5 (black dashed line in D) shows meningeal, vascular expression. F. Transverse section through e7.5 rostral hindbrain (white dashed line in D) showing expression in the meninges (*) and blood vessels.

Mentions: To examine the Raldh-independent generation of RA, we also analysed the expression of mRNA transcripts for the cytochrome p450 RA-synthesising enzyme, Cyp1B1 [36]. Expression of Cyp1B1 is found in the developing meningeal membranes at e5. In contrast to Raldh2, dorsoventral distribution of Cyp1B1 is uniform (Fig. 4A). Transverse sections reveal Cyp1B1 expression in blood vessels and the adjacent cranial mesoderm (Fig. 4B). Cyp1B1 is also expressed at the rhombic lip from e4.5 (Fig. 4C). Expression in the meninges and blood vessels is maintained to e7.5 and beyond (Fig. 4D–F).


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)

Expression of Cyp1B1. A. Cyp1B1 expression at e5 is located in the developing meninges (*). B. Transverse section through the cerebellar region (black dashed line in A) shows expression in the blood vessels within the neural tube (arrow) and the cranial mesenchyme (*). C. Transverse section through the rostral hindbrain (white dashed line in A) reveals expression at the rhombic lip (inset at higher magnification).D. Meningeal membrane expression at e7.5 (*). E. Transverse section through cerebellum at e7.5 (black dashed line in D) shows meningeal, vascular expression. F. Transverse section through e7.5 rostral hindbrain (white dashed line in D) showing expression in the meninges (*) and blood vessels.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 4: Expression of Cyp1B1. A. Cyp1B1 expression at e5 is located in the developing meninges (*). B. Transverse section through the cerebellar region (black dashed line in A) shows expression in the blood vessels within the neural tube (arrow) and the cranial mesenchyme (*). C. Transverse section through the rostral hindbrain (white dashed line in A) reveals expression at the rhombic lip (inset at higher magnification).D. Meningeal membrane expression at e7.5 (*). E. Transverse section through cerebellum at e7.5 (black dashed line in D) shows meningeal, vascular expression. F. Transverse section through e7.5 rostral hindbrain (white dashed line in D) showing expression in the meninges (*) and blood vessels.
Mentions: To examine the Raldh-independent generation of RA, we also analysed the expression of mRNA transcripts for the cytochrome p450 RA-synthesising enzyme, Cyp1B1 [36]. Expression of Cyp1B1 is found in the developing meningeal membranes at e5. In contrast to Raldh2, dorsoventral distribution of Cyp1B1 is uniform (Fig. 4A). Transverse sections reveal Cyp1B1 expression in blood vessels and the adjacent cranial mesoderm (Fig. 4B). Cyp1B1 is also expressed at the rhombic lip from e4.5 (Fig. 4C). Expression in the meninges and blood vessels is maintained to e7.5 and beyond (Fig. 4D–F).

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