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Fig. 4. SRp38 inhibits the activity of neurogenin but not that of neuroD. (A) SRp38
blocks neurogenin induction of neuroD. Stage 15 lateral view, neuroD
in situ hybridization. Control embryo: normal expression pattern of
neuroD (in trigeminal ganglia indicated by red arrowhead). Expression
of 500 pg SRp38 inhibits neuroD expression. However, expression of
250 pg of neurogenin induces ectopic expression of neuroD,
while co-expression of SRp38 with neurogenin inhibits induction of
neuroD (right embryo). (B) Ectodermal explant RT-PCR. SRp38 blocks
neurogenin induction of NCAM, neuronal ß-tubulin,
synaptobrevin II and neuroD. Analysis of animal caps expressing
either 500 pg of SRp38 and/or 250 pg neurogenin as
indicated. EF1
is a loading control and muscle actin
(mActin) controls for mesodermal contamination. (C) SRp38 does not block
neuroD induction of synaptobrevin II (sybII). Stage 25
embryos stained for sybII. Control embryo: normal expression pattern
of sybII in trigeminal ganglia and neurons. Expression of 500 pg
SRp38 inhibits sybII expression. Ectopic expression of 250pg of
neuroD induces ectopic expression of for sybII, while co-expression
of SRp38 with neuroD does not inhibit neuroD induction of sybII. (D)
Simplified schematic of neurogenic cascade. In the neural plate, neurogenin
activates transcription of several downstream genes, including
neuroD. neuroD then induces genes characteristic of neuronal
differentiation such as neuronal ß-tubulin and
synaptobrevin. Notch signaling can inhibit the neurogenic effects of
neurogenin but not neuroD.