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Specification of the lens and olfactory placodes and dorsoventral patterning of the telencephalon
Umeå University, Faculty of Medicine, Umeå Centre for Molecular Medicine (UCMM).
2007 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The vertebrate nervous system is a highly complex and intriguing structure with diverse functions. To understand the functional nervous system, we first have to be aware of how it is assembled during development. In this thesis the mechanism of early diversification and regionalisation necessary for subsequent formation of part of the nervous system, namely the telencephalon and the placodes, will be addressed. We have identified signalling molecules involved in the dorsoventral patterning of the telencephalon and we propose a mechanism for the induction and differential specification of the olfactory and lens placodes.

The telencephalon is regionalised along the dorsoventral axis during development. The cells situated dorsally will give rise to the cerebral cortex while the ventral and intermediate cells are mainly progenitors for the basal ganglia. The cerebral cortex is associated with higher cognitive functions whereas the basal ganglia control movements. We provide evidence that dorsal and intermediate telencephalic cells are re-specified from cells with an intrinsic ventral character. Dorsal telencephalic cells are specified at stage 10 in chick, while the intermediate cells are specified a few hours later, at stage 14. The expression of Wnt and Fibroblast growth factors (Fgfs) coincides with the time point when the dorsal cells are specified, and we provide evidence that Wnt and FGF signals act in a sequential way to specify dorsal telencephalic cells. The retinoic acid (RA) synthesising enzyme Raldh3 is expressed in proximity to the telencephalon, and our result suggests that RA is both required and sufficient to induce intermediate telencephalic cell types. Additionally, Fgf8 is expressed in the anterior neural ridge and the ventral telencephalic cells require FGF signals that oppose RA to maintain their character.

The olfactory and lens placodes contribute to the special sense organs associated with olfaction and vision, respectively. Olfactory and lens placodes are specified at gastrula stage in chick, and become spatially separated at the neural fold stage. We provide evidence that Bone morphogenetic protein (BMP) signalling is required for the induction of a pool of placodal progenitor cells. Furthermore, time of exposure to BMP signals plays a key role in the differential specification of the olfactory and lens placodes, where continued exposure to BMP signals promotes lens character at the expense of olfactory placodal cells.

Place, publisher, year, edition, pages
Umeå: Umeå centrum för molekylär medicin (UCMM) , 2007. , 77 p.
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 1119
Keyword [en]
telencephalon, olfactory, lens, BMP, RA, FGF, Wnt, development, placode, gradient, chick, nervous system, dorsoventral
Research subject
Developmental Neurosciences
Identifiers
URN: urn:nbn:se:umu:diva-1347ISBN: 978-91-7264-376-5 (print)OAI: oai:DiVA.org:umu-1347DiVA: diva2:140719
Public defence
2007-10-05, Major Groove, 6L, NUS, Umeå, 13:00 (English)
Opponent
Available from: 2007-09-13 Created: 2007-09-13 Last updated: 2009-09-24Bibliographically approved
List of papers
1. Specification of dorsal telencephalic character by sequential Wnt and FGF signaling.
Open this publication in new window or tab >>Specification of dorsal telencephalic character by sequential Wnt and FGF signaling.
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2003 (English)In: Nature Neuroscience, ISSN 1097-6256, Vol. 6, no 7, 701-707 p.Article in journal (Refereed) Published
Abstract [en]

Dorsoventral patterning of the telencephalon is established early in forebrain development and underlies many of the regional subdivisions that are critical to the later organization of neural circuits in the cerebral cortex and basal ganglia. Sonic hedgehog (Shh) is involved in the generation of the ventral-most telencephalic cells, but the identity of the extrinsic signal(s) that induce dorsal character in telencephalic cells is not known. Here we show in chick embryos that sequential Wnt and fibroblast growth factor (FGF) signaling specifies cells of dorsal telencephalic character.

Keyword
Aging/genetics/metabolism, Animals, Basic Helix-Loop-Helix Transcription Factors, Bone Morphogenetic Proteins/physiology, Cell Differentiation, Chick Embryo, Ectoderm/cytology/physiology, Embryonic Induction/*physiology, Epithelium, Eye Proteins, Fibroblast Growth Factors/classification/genetics/*physiology, Frizzled Receptors, Gene Expression Regulation; Developmental, Homeodomain Proteins/genetics/metabolism, Immunohistochemistry, In Situ Hybridization/methods, Mice, Nerve Tissue Proteins/genetics/metabolism, Organ Culture Techniques, Paired Box Transcription Factors, Proteins/physiology, Proto-Oncogene Proteins/genetics/*physiology, Pyrroles/pharmacology, Receptors; Fibroblast Growth Factor/physiology, Repressor Proteins, Signal Transduction/genetics/*physiology, Stem Cells/metabolism, Telencephalon/cytology/embryology/metabolism/*physiology, Transcription Factors, Wnt Proteins, Zebrafish Proteins
Identifiers
urn:nbn:se:umu:diva-5932 (URN)10.1038/nn1068 (DOI)12766771 (PubMedID)
Available from: 2007-12-03 Created: 2007-12-03 Last updated: 2009-11-25Bibliographically approved
2. Retinoic acid signalling specifies intermediate character in the developing telencephalon.
Open this publication in new window or tab >>Retinoic acid signalling specifies intermediate character in the developing telencephalon.
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2004 (English)In: Development, ISSN 0950-1991, Vol. 131, no 17, 4323-4332 p.Article in journal (Refereed) Published
Abstract [en]

The organisation of the telencephalon into its major structures depends on its early regionalisation along the dorsoventral axis. Previous studies have provided evidence that sonic hedgehog (SHH) is required for the generation of telencephalic cells of ventral character, and that sequential WNT and fibroblast growth factor (FGF) signalling specifies cells of dorsal telencephalic character. However, the signalling mechanisms that specify telencephalic cells of an intermediate character remain to be defined. We provide evidence here that retinoic acid has a crucial role in specifying telencephalic progenitor cells of intermediate character.

Keyword
Animals, Cell Division, Chick Embryo, Cloning; Molecular, DNA; Complementary/metabolism, Fibroblast Growth Factors/metabolism, Homeodomain Proteins/genetics/metabolism, Immunohistochemistry, In Situ Hybridization, Mice, Models; Biological, Organ Culture Techniques, Protein Structure; Tertiary, Signal Transduction, Telencephalon/*embryology/metabolism, Time Factors, Trans-Activation (Genetics), Transcription Factors, Tretinoin/*metabolism
Identifiers
urn:nbn:se:umu:diva-5816 (URN)10.1242/dev.01308 (DOI)15294870 (PubMedID)
Available from: 2007-11-30 Created: 2007-11-30 Last updated: 2009-11-25Bibliographically approved
3. Time of exposure to BMP signals plays a key role in the specification of the olfactory and lens placodes ex vivo.
Open this publication in new window or tab >>Time of exposure to BMP signals plays a key role in the specification of the olfactory and lens placodes ex vivo.
2007 (English)In: Developmental Cell, ISSN 1534-5807, Vol. 13, no 1, 141-149 p.Article in journal (Refereed) Published
Keyword
Animals, Bone Morphogenetic Proteins/*metabolism, Cell Differentiation/physiology, Chick Embryo, Ectoderm/cytology/metabolism, Fibroblast Growth Factors/metabolism, Lens; Crystalline/cytology/*embryology/metabolism, Neurons/cytology/metabolism, Olfactory Pathways/cytology/*embryology/metabolism, Signal Transduction/*physiology, Stem Cells/cytology/metabolism
Identifiers
urn:nbn:se:umu:diva-5807 (URN)10.1016/j.devcel.2007.04.020 (DOI)17609116 (PubMedID)
Available from: 2007-11-30 Created: 2007-11-30 Last updated: 2009-09-24Bibliographically approved

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