Complex and dynamic patterns of Wnt pathway gene expression in the developing chick forebrain.
BACKGROUND
Wnt signalling regulates multiple aspects of brain development in vertebrate embryos. A large number of Wnts are expressed in the embryonic forebrain; however, it is poorly understood which specific Wnt performs which function and how they interact. Wnts are able to activate different intracellular pathways, but which of these pathways become activated in different brain subdivisions also remains enigmatic.


RESULTS
We have compiled the first comprehensive spatiotemporal atlas of Wnt pathway gene expression at critical stages of forebrain regionalisation in the chick embryo and found that most of these genes are expressed in strikingly dynamic and complex patterns. Several expression domains do not respect proposed compartment boundaries in the developing forebrain, suggesting that areal identities are more dynamic than previously thought. Using an in ovo electroporation approach, we show that Wnt4 expression in the thalamus is negatively regulated by Sonic hedgehog (Shh) signalling from the zona limitans intrathalamica (ZLI), a known organising centre of forebrain development.


CONCLUSIONS
The forebrain is exposed to a multitude of Wnts and Wnt inhibitors that are expressed in a highly dynamic and complex fashion, precluding simple correlative conclusions about their respective functions or signalling mechanisms. In various biological systems, Wnts are antagonised by Shh signalling. By demonstrating that Wnt4 expression in the thalamus is repressed by Shh from the ZLI we reveal an additional level of interaction between these two pathways and provide an example for the cross-regulation between patterning centres during forebrain regionalisation.
Quinlan
Robyn
R
MRC Centre for Developmental Neurobiology, New Hunt's House, Guy's Hospital Campus, King's College, London SE1 1UL, UK. rquinlan@ich.ucl.ac.uk
Graf
Manuela
M
Mason
Ivor
I
Lumsden
Andrew
A
Kiecker
Clemens
C
D000818:Animals; D030161:Avian Proteins / Q000235:genetics / Q000378:metabolism*; D002642:Chick Embryo; D004027:Diencephalon / Q000196:embryology / Q000378:metabolism; D018274:Electroporation; D005110:Extracellular Space / Q000378:metabolism; D051157:Frizzled Receptors / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D053823:Hedgehog Proteins / Q000378:metabolism; D017403:In Situ Hybridization; D042541:Intracellular Space / Q000378:metabolism; D016548:Prosencephalon / Q000196:embryology* / Q000378:metabolism*; D015398:Signal Transduction; D013788:Thalamus / Q000196:embryology / Q000378:metabolism; D013997:Time Factors; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*
D030161:Avian Proteins; D051157:Frizzled Receptors; D053823:Hedgehog Proteins; D051153:Wnt Proteins; D049452:Green Fluorescent Proteins