First published online June 28, 2004
Development 131, 1405e (2004)
© The Company of Biologists Limited
Essential enhancers in the head
Otx2 is a paired-type homeobox gene expressed at every step of
tetrapod head development – in the epiblast (EP), the distal anterior
visceral endoderm, the anterior mesendoderm, the anterior neuroectoderm (AN),
the entire forebrain and midbrain, and the cephalic mesenchyme. However,
because Otx2 is essential for mouse head development, it is difficult
to distinguish the functions that it performs at these different stages. In
two papers in this issue, Aizawa and colleagues describe the enhancers
responsible for Otx2 expression in the EP and the AN
(p. 3307), and in the
forebrain and midbrain (p.
3319). The EP enhancer is active in the EP at E5.5 and the AN
enhancer is active in the AN from E7.0 until E8.5. By mutating the AN enhancer
in vivo, the researchers found that it is required for the maintenance of the
AN during development. Unexpectedly, although the AN gives rise to the
forebrain and midbrain, Otx2 expression in the forebrain and midbrain
is not regulated by the AN enhancer, but by two other distinct enhancers: FM
and FM2. In their second paper, the researchers show that this switch in
enhancer activity occurs between E8.0 and E8.5, corresponding to the stage at
which the boundary between the midbrain and the hindbrain is established.
Furthermore, the development of these regions is regulated differentially in a
dose-dependent manner; higher levels of Otx2 appear to be required for the
development of more posterior portions of the forebrain/midbrain. Aizawa and
colleagues maintain that these results represent a starting point for finding
the many unknown factors that regulate these enhancers. They also consider the
conservation of these enhancer sequences across mouse, human, Xenopus
and zebrafish, and discuss the future work required to determine the
phylogenetic significance of Otx2 enhancer organisation.
Related articles in Development:
- Regulation of Otx2 expression and its functions in mouse epiblast and anterior neuroectoderm
- Daisuke Kurokawa, Nobuyoshi Takasaki, Hiroshi Kiyonari, Rika Nakayama, Chiharu Kimura-Yoshida, Isao Matsuo, and Shinichi Aizawa
Development 2004 131: 3307-3317.
[Abstract]
[Full Text]
- Regulation of Otx2 expression and its functions in mouse forebrain and midbrain
- Daisuke Kurokawa, Hiroshi Kiyonari, Rika Nakayama, Chiharu Kimura-Yoshida, Isao Matsuo, and Shinichi Aizawa
Development 2004 131: 3319-3331.
[Abstract]
[Full Text]
