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An early role for WNT signaling in specifying neural patterns of Cdx and Hox gene expression and motor neuron subtype identity
Umeå University, Faculty of Medicine, Umeå Centre for Molecular Medicine (UCMM).
Umeå University, Faculty of Medicine, Umeå Centre for Molecular Medicine (UCMM).
Umeå University, Faculty of Medicine, Umeå Centre for Molecular Medicine (UCMM).
2006 (English)In: PLoS biology, ISSN 1544-9173, E-ISSN 1545-7885, Vol. 4, no 8, 1438-1452 p.Article in journal (Refereed) Published
Abstract [en]

The link between extrinsic signaling, progenitor cell specification and neuronal subtype identity is central to the developmental organization of the vertebrate central nervous system. In the hindbrain and spinal cord, distinctions in the rostrocaudal identity of progenitor cells are associated with the generation of different motor neuron subtypes. Two fundamental classes of motor neurons, those with dorsal (dMN) and ventral (vMN) exit points, are generated over largely non-overlapping rostrocaudal domains of the caudal neural tube. Cdx and Hox genes are important determinants of the rostrocaudal identity of neural progenitor cells, but the link between early patterning signals, neural Cdx and Hox gene expression, and the generation of dMN and vMN subtypes, is unclear. Using an in vitro assay of neural differentiation, we provide evidence that an early Wnt-based program is required to interact with a later retinoic acid- and fibroblast growth factor–mediated mechanism to generate a pattern of Cdx and Hox profiles characteristic of hindbrain and spinal cord progenitor cells that prefigure the generation of vMNs and dMNs.

Place, publisher, year, edition, pages
Public library of science , 2006. Vol. 4, no 8, 1438-1452 p.
Keyword [en]
Animals, Avian Proteins/genetics/metabolism, Central Nervous System/*embryology, Chick Embryo, Fibroblast Growth Factors/metabolism, Gene Expression Regulation; Developmental, Genes; Homeobox, Homeodomain Proteins/genetics/*metabolism, Motor Neurons/*cytology/metabolism, Rhombencephalon/cytology/embryology/metabolism, Signal Transduction, Spinal Cord/cytology/embryology/metabolism, Stem Cells/cytology/metabolism, T-Box Domain Proteins/genetics/metabolism, Tretinoin/metabolism, Wnt Proteins/genetics/*metabolism
National Category
Cell and Molecular Biology
URN: urn:nbn:se:umu:diva-5811DOI: 10.1371/journal.pbio.0040252ISI: 000240007400015PubMedID: 16895440OAI: diva2:145479
Available from: 2007-11-30 Created: 2007-11-30 Last updated: 2014-06-16Bibliographically approved
In thesis
1. Early development of the olfactory placode and early rostrocaudal patterning of the caudal neural tube
Open this publication in new window or tab >>Early development of the olfactory placode and early rostrocaudal patterning of the caudal neural tube
2009 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The development of the nervous system is a complex process. Cell divisions, cell differentiation and signalling interactions must be tightly regulated. To comprehend the mature nervous system, we have to understand its assembly during development. Two main questions were addressed in this thesis: (1) how is the caudal part of the central nervous system specified and (2) how is the early development of the olfactory placode regulated? By using tissue and whole embryo assays in the chick, we identified signalling molecules involved in these processes and propose possible mechanisms for their function.

The central nervous system is regionalized along its rostrocaudal axis during development. However, the mechanisms by which cells in the caudal part of the neuraxis acquire rostrocaudal regional identity have been unresolved. We provide evidence that at gastrula stages cells in the caudal neural plate are specified as cells of caudal spinal cord character in response to Wnt and FGF signals and that cells of rostral spinal cord and caudal hindbrain character only emerge later at neurulation stages in response to retinoic acid signalling acting on previously caudalized cells. In the hindbrain and spinal cord distinct motor neuron subtypes differentiate at precise rostrocaudal positions from progenitor cells. We provide evidence that cells in the caudal neural plate have acquired sufficient positional information to differentiate into motor neurons of the correct rostrocaudal subtype.

The olfactory placode gives rise to all the structures of the peripheral olfactory system, which, in the chick consists of the olfactory nerve, the sensory epithelium, where the olfactory sensory neurons (OSN) are located and the respiratory epithelium, that produces the mucus. Several studies have addressed the role of signalling cues in the specification of OSNs but much less is known about the regulation of sensory versus respiratory patterning and the events controlling early neurogenesis in the developing olfactory placode.

We show that by stage 14 the olfactory placode is specified to give rise to both cells of sensory and respiratory epithelial character. Moreover, cells of respiratory epithelial character require BMP signalling, whereas cells of sensory epithelial character require FGF signalling. We suggest a mechanism in which FGF and BMP signals act in an opposing manner to regulate olfactory versus respiratory epithelial cell fate decision. BMP signalling has also been implicated in the regulation of neurogenesis in the sensory epithelium, and we show that BMP signals are required for the generation of OSNs, because in the absence of BMP signalling cells in the sensory epithelium do not mature.

Independently, we also analyzed the role of Notch signalling during early olfactory development both in vitro and in vivo and provide evidence that active Notch signalling is required to prevent cells in the olfactory placode from premature differentiation.

Place, publisher, year, edition, pages
Umeå: Umeå centre for molecular medicine (UCMM), 2009. 67 p.
Umeå University medical dissertations, ISSN 0346-6612 ; 1274
olfactory placode, caudal neural tube, Wnt, FGF, RA, BMP, Notch, patterning
National Category
Developmental Biology
Research subject
Molecular Biology
urn:nbn:se:umu:diva-22622 (URN)978-91-7264-804-3 (ISBN)
Umeå centrum för molekylär medicin (UCMM), 90185, Umeå
Public defence
2009-06-13, Betula, Norrlands universitetssjukhus, Umeå, 09:00 (English)
Available from: 2009-05-19 Created: 2009-05-14 Last updated: 2010-01-18Bibliographically approved

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