Segmental identity and cerebellar granule cell induction in rhombomere 1
<p>Abstract</p> <p>Background</p> <p>Cerebellar granule cell precursors are specifically generated within the hindbrain segment, rhombomere 1, which is bounded rostrally by the midbrain/hindbrain isthmus and caudally by the boundary of the <it>Hoxa2 </it>exp...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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BMC
2004-06-01
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| Series: | BMC Biology |
| Online Access: | http://www.biomedcentral.com/1741-7007/2/14 |
| _version_ | 1811251142754041856 |
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| author | Bell Esther Toole Leah Eddison Mark Wingate Richard JT |
| author_facet | Bell Esther Toole Leah Eddison Mark Wingate Richard JT |
| author_sort | Bell Esther |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Cerebellar granule cell precursors are specifically generated within the hindbrain segment, rhombomere 1, which is bounded rostrally by the midbrain/hindbrain isthmus and caudally by the boundary of the <it>Hoxa2 </it>expression domain. While graded signals from the isthmus have a demonstrable patterning role within this region, the significance of segmental identity for neuronal specification within rhombomere 1 is unexplored. We examined the response of granule cell precursors to the overexpression of <it>Hoxa2</it>, which normally determines patterns of development specific to the hindbrain. How much does the development of the cerebellum, a midbrain/hindbrain structure, reflect its neuromeric origin as a hindbrain segment?</p> <p>Results</p> <p>We show that a <it>Gbx2</it>-positive, <it>Otx2</it>-/<it>Hoxa2</it>-negative territory corresponding to rhombomere 1 forms prior to an identifiable isthmic organiser. Early global overexpression of <it>Hoxa2 </it>at embryonic day 0 has no effect on the expression of isthmic signalling molecules or the allocation of rhombomere 1 territory, but selectively results in the loss of granule cell markers at embryonic day 6 and the depletion of cell bodies from the external granule cell layer. By comparison the trochlear nucleus and locus coeruleus form normally in ventral rhombomere 1 under these conditions. Microsurgery, coupled with electroporation, to target <it>Hoxa2 </it>overexpression to rhombic lip precursors, reveals a profound, autonomous respecification of migration. Rhombic lip derivatives, normally destined to occupy the external granule cell layer, violate the cerebellar boundary to form a ventrolateral nucleus in a position comparable to that occupied by rhombic lip derived neurons in rhombomere 2.</p> <p>Conclusions</p> <p>Different overexpression strategies reveal that the recognition of migration cues by granule cell precursors is dependent on their identity as rhombomere 1 derivatives. Segmental patterning cues operate autonomously within the rhombic lip precursor pool. By contrast, a subset of coextensive nuclei is refractory to ectopic <it>Hoxa2 </it>and is presumably induced solely by isthmic organiser activity. Thus, graded (isthmic) and segmental mechanisms may operate exclusively of one another in the specification of different neuronal populations within rhombomere 1. The early designation of an <it>Otx2</it>-negative, <it>Hoxa2</it>-negative region, prior to the appearance of the isthmic organiser, is a key initial step in the specification of the cerebellum.</p> |
| first_indexed | 2024-04-12T16:15:18Z |
| format | Article |
| id | doaj.art-3afd2d80dfd84fcbb3c8c8e1df09c938 |
| institution | Directory Open Access Journal |
| issn | 1741-7007 |
| language | English |
| last_indexed | 2024-04-12T16:15:18Z |
| publishDate | 2004-06-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Biology |
| spelling | doaj.art-3afd2d80dfd84fcbb3c8c8e1df09c9382022-12-22T03:25:44ZengBMCBMC Biology1741-70072004-06-01211410.1186/1741-7007-2-14Segmental identity and cerebellar granule cell induction in rhombomere 1Bell EstherToole LeahEddison MarkWingate Richard JT<p>Abstract</p> <p>Background</p> <p>Cerebellar granule cell precursors are specifically generated within the hindbrain segment, rhombomere 1, which is bounded rostrally by the midbrain/hindbrain isthmus and caudally by the boundary of the <it>Hoxa2 </it>expression domain. While graded signals from the isthmus have a demonstrable patterning role within this region, the significance of segmental identity for neuronal specification within rhombomere 1 is unexplored. We examined the response of granule cell precursors to the overexpression of <it>Hoxa2</it>, which normally determines patterns of development specific to the hindbrain. How much does the development of the cerebellum, a midbrain/hindbrain structure, reflect its neuromeric origin as a hindbrain segment?</p> <p>Results</p> <p>We show that a <it>Gbx2</it>-positive, <it>Otx2</it>-/<it>Hoxa2</it>-negative territory corresponding to rhombomere 1 forms prior to an identifiable isthmic organiser. Early global overexpression of <it>Hoxa2 </it>at embryonic day 0 has no effect on the expression of isthmic signalling molecules or the allocation of rhombomere 1 territory, but selectively results in the loss of granule cell markers at embryonic day 6 and the depletion of cell bodies from the external granule cell layer. By comparison the trochlear nucleus and locus coeruleus form normally in ventral rhombomere 1 under these conditions. Microsurgery, coupled with electroporation, to target <it>Hoxa2 </it>overexpression to rhombic lip precursors, reveals a profound, autonomous respecification of migration. Rhombic lip derivatives, normally destined to occupy the external granule cell layer, violate the cerebellar boundary to form a ventrolateral nucleus in a position comparable to that occupied by rhombic lip derived neurons in rhombomere 2.</p> <p>Conclusions</p> <p>Different overexpression strategies reveal that the recognition of migration cues by granule cell precursors is dependent on their identity as rhombomere 1 derivatives. Segmental patterning cues operate autonomously within the rhombic lip precursor pool. By contrast, a subset of coextensive nuclei is refractory to ectopic <it>Hoxa2 </it>and is presumably induced solely by isthmic organiser activity. Thus, graded (isthmic) and segmental mechanisms may operate exclusively of one another in the specification of different neuronal populations within rhombomere 1. The early designation of an <it>Otx2</it>-negative, <it>Hoxa2</it>-negative region, prior to the appearance of the isthmic organiser, is a key initial step in the specification of the cerebellum.</p>http://www.biomedcentral.com/1741-7007/2/14 |
| spellingShingle | Bell Esther Toole Leah Eddison Mark Wingate Richard JT Segmental identity and cerebellar granule cell induction in rhombomere 1 BMC Biology |
| title | Segmental identity and cerebellar granule cell induction in rhombomere 1 |
| title_full | Segmental identity and cerebellar granule cell induction in rhombomere 1 |
| title_fullStr | Segmental identity and cerebellar granule cell induction in rhombomere 1 |
| title_full_unstemmed | Segmental identity and cerebellar granule cell induction in rhombomere 1 |
| title_short | Segmental identity and cerebellar granule cell induction in rhombomere 1 |
| title_sort | segmental identity and cerebellar granule cell induction in rhombomere 1 |
| url | http://www.biomedcentral.com/1741-7007/2/14 |
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