The transcription factor Pax6 affects cell fate, cell proliferation and patterning during brain development in many species. But how are these diverse effects regulated? Haubst and co-workers now report that neurogenesis, cell proliferation and patterning are all severely abnormal in the forebrain of mice carrying a deletion in the Pax6 paired-domain (PD), a DNA-binding domain(see p. 6131). Thus,the PD of Pax6 plays a key role in brain development. Several splice variants of Pax6 exist, including Pax6(5a), a splice variant in which a 14 amino acid insert in the PD affects the DNA consensus sequence to which the PD binds. Experiments in which Pax6 or Pax6(5a) are overexpressed in vitro indicate that, whereas Pax6 regulates both cell fate and proliferation, Pax6(5a)regulates cell proliferation only. Splicing may, therefore, control the diverse developmental roles of Pax6 by affecting the target genes to which it binds.

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2004