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Fig. 8. A schematic representation of a possible model of genes and interactions
involved in CGC development. Early cerebellar dorsoventral patterning genes
and pathways involved in determination of hindbrain boundaries and fate
specification, like BMPs, sonic hedgehog (SHH) and Notch are presented
(reviewed by Wang and Zoghbi,
2001 ). Specifically, Bmp7 was shown to activate
Math1 and Zic1 expression
(Alder et al., 1999).
Math1 is subjected to further positive autoactivation through binding
to an E-box motif in a downstream enhancer
(Helms et al., 2000). However,
Math1 transcription and binding activities are known to be
downregulated by the Hes gene products
(Akazawa et al., 1995). As
shown here, Math1 may also have a negative autoregulatory loop,
through a direct or indirect transcriptional activation of Hes5,
which further elevates the level of Hes5, leading to downregulation
of its transcription. Moreover, Zic1 can bind directly to
Math1 enhancer and repress Math1 positive autoregulation
(Ebert et al., 2003). However,
we assume that unidentified Math1 target genes are also involved in a
complete attenuation of Math1 expression, cell cycle exit and further
differentiation. White arrows indicate transcription, and blue and red arrows
indicate activation and suppression, respectively. Broken arrows indicate
pathways that act up- and downstream of CGC transcription factors.
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