Fig. 6. Nmyc (N-myc in figure) is upregulated in proliferating neural tube precursors exposed to Shh and in medulloblastoma.

(A-D) Hybridization for Nmyc and Shh mRNA transcripts was carried out in situ on adjacent transverse sections of spinal cord of 12.5 dpc wild-type (A) and Shh transgenic (Rowitch et al., 1999) embryos, which overexpress Shh in the dorsal neural tube (boxed) (C).

(B,D) Nmyc is upregulated within proliferating neural precursors exposed to ectopic Shh (red box in D). Note that Nmyc is not a general Shh transcriptional target, because expression is absent in the floorplate (fp) where Shh is strongly expressed (compare A, arrow, with B).

Additionally, Nmyc can be activated by mitogens other than Shh. Nmyc expression is observed in the dorsal spinal cord and dorsal root ganglion (drg) in the absence of adjacent Shh expression (compare B, arrow, with A; compare D with C). Thus, Nmyc is upregulated by Shh only in proliferating precursor cells. (E,F) Nmyc is upregulated in medulloblastomas of adult Ptch heterozygotes. Representative results of analysis of four animals are shown. (E) The normal adult cerebellum is devoid of Nmyc expression is at left in this image. By contrast, the tumor tissue expresses Nmyc strongly. (F) High-power view of boxed region in E shows possible area of continuity of the strongly Nmyc-expressing tumor cells (arrow) with the internal granule layer (IGL) and disruption of the molecular layer (Mol). The broken dashed line indicates the boundary between normal cerebellar tissue and medulloblastoma. ant, anterior; post, posterior; IV, fourth ventricle; cp, choroid plexus.

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