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Genes and Development
Vol. 11, No. 15,
pp. 1925-1937,
August 1, 1997
1 Department of Cell Biology, and
4 Medicine,
Baylor College of Medicine, Houston, Texas 77030 USA
The COUP-TFs are orphan members of the
steroid/thyroid hormone receptor superfamily. Multiple
COUP-TF members have been cloned and they share a high degree of
sequence homology between species as divergent as Drosophila
and humans, suggesting a conservation of function through evolution.
The COUP-TFs are highly expressed in the developing nervous systems of
several species examined, indicating their possible involvement in
neuronal development and differentiation. In the mouse, there are two
very homologous COUP-TF genes (I and II) and their expression patterns
overlap extensively. To study the physiological function of mCOUP-TFI, a gene-targeting approach was undertaken. We report here that mCOUP-TFI
null animals die perinataly. Mutant embryos display an altered
morphogenesis of the ninth cranial ganglion and nerve. The aberrant
formation of the ninth ganglion is most possibly attributable to extra
cell death in the neuronal precursor cell population. In addition, at
midgestation, aberrant nerve projection and arborization were oberved
in several other regions of mutant embryos. These results indicate that
mCOUP-TFI is required for proper fetal development and is essential for
postnatal development. Furthermore, mCOUP-TFI possesses vital
physiological functions that are distinct from mCOUP-TFII despite of
their high degree of homology and extensive overlapping expression
patterns.
[Key Words: COUP-TF; glossopharyngeal ganglion; axonal projection; arborization]
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