We have previously shown that the arcuate organization of cell fates within the
ventral midbrain critically depends upon the morphogen, Sonic Hedgehog (SHH), which
is secreted from a signaling center located along the ventral midline, called the floor
plate (FP). Thus, it is ultimately the specification of the FP that is responsible for the
patterning and specification of ventral midbrain cell fates. Interestingly, we have found
that the chick midbrain FP can be divided into medial (MFP) and lateral (LFP) regions on
the basis of gene expression, mode of induction and function. Overexpression of SHH
alone is sufficient to recapitulate the entire pattern of ventral cell fates, although
remarkably it cannot induce MFP, consistent with the observation that the MFP is
refractory to any perturbations of HH signaling. In contrast, overexpression of the
winged-helix transcription factor FOXA2/HNF3[beta]robustly induced the MFP fate throughout ventral midbrain while blocking its activity resulted in the absence of the
MFP. Thus, by analyzing the differences between SHH and FOXA2 blockade and
overexpression, we were able to attribute functions to each the LFP and the MFP.
Notably, we observed that FOXA2 overexpression caused a bending of the midbrain
neurepithelium that resembled the endogenous median hinge-point observed during
neurulation. Additionally, FOXA2 misexpression led to a robust induction of DA
progenitors and neurons that was never observed after SHH expression alone. In
contrast, we found that all other ventral cell types required HH signaling directly, at a
distance and early on in the development of the midbrain when its tissue size is relatively
small. Additionally, HH blockade resulted in increased cell-scatter of the arcuate
territories and in the disruption of the regional boundaries between the ventral midbrain
and adjacent tissue. Thus, we bring new insight into the mechanism by which midbrain
FP is specified and ascribe functional roles to its subregions. We propose that while the
MFP regulates the production of dopaminergic progenitors and the changes in cellshape
required for bending and shaping the neural tube, the LFP appears to be largely
responsible for cell survival and the formation of a spatially coherent pattern of midbrain
cell fates. / text
| Identifer | oai:union.ndltd.org:UTEXAS/oai:repositories.lib.utexas.edu:2152/6531 |
| Date | 15 October 2009 |
| Creators | Bayly, Roy Downer, 1981- |
| Source Sets | University of Texas |
| Language | English |
| Detected Language | English |
| Format | electronic |
| Rights | Copyright is held by the author. Presentation of this material on the Libraries' web site by University Libraries, The University of Texas at Austin was made possible under a limited license grant from the author who has retained all copyrights in the works. |
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