|
|
|
|
|
|
|
||||
| Home Help Feedback Subscriptions Archive Search Table of Contents | ||||
|
Fig. 3. Helt selects the GABAergic versus glutamatergic phenotype in the
mesencephalon. (A) Gene targeting strategy. All exons encoding the
Helt ORF were replaced with a GFP cDNA, and recombination
was confirmed by Southern blotting (data not shown). The null phenotype in
homozygous mutant mouse embryos was confirmed by complete loss of Helt
expression (right-hand panels). (B) Helt is required for
induction of GABAergic neurons and suppression of glutamatergic
differentiation. In the Helt-/- mutant mesencephalon,
Gad1+ neurons are only detected in the ventral-most m5
region of the presumptive GABAergic domains, whereas
Vglut2+ neurons are generated in essentially all domains
of the mesencephalon at E11.5. At E12.5, although Gad1+
neurons start to emerge in a broad area of the ventral GABAergic domains (m3
to m5), the frequency is still lower than that in wild-type control embryos
and ectopic Vglut2+ neurogenesis continues. Dorsal
Gad1+ neurons are completely absent in the mutants.
(C) Helt suppresses glutamatergic neurogenesis and induces GABAergic
neurons. In the transgenic embryos expressing Helt under the control
of the nestin enhancer, the number of Vglut2+ cells is
decreased and the number of Gad1+ cells is increased
instead. Note that GABAergic neurons are efficiently generated and
glutamatergic neurons are suppressed in the ML just outside of the VZ positive
for exogenous Helt, suggesting a cell-autonomous effect of Helt.
|
