[Abstract Title]. - Society for Neuroscience

Endocrine Society Bridge Award
Title: Fibroblast growth factor 8 deficiency affects olfactory placode morphogenesis from which
gonadotropin-releasing hormone neurons emerge
Authors: *W. C. CHUNG, P.-S. TSAI;
Dept Integrative Physiol, Univ. Colorado Boulder, Boulder, CO
Abstract: Gonadotropin-releasing hormone (GnRH) neurons are scattered throughout the
preoptic-hypothalamus and represent the most upstream neuroendocrine regulators of the
hypothalamus-pituitary-gonadal axis. Previous studies showed that mouse GnRH neurons are
first detected in the olfactory placode (OP) around embryonic day (E) 10.5-11.5. Recently, we
showed that GnRH neurons failed to emerge from the olfactory placode (OP) of E11.5 mouse
embryos hypomorphic for fibroblast growth factor (FGF) 8. To better understand the mechanism
underlying this disruption, we examined the morphogenesis of the OP in E11.5 Fgf8
hypomorphs. First, we examined whether FGF8 deficiency causes a general dysgenesis of the
olfactory epithelium (OE) by verifying the presence of Olf-1 (a marker for olfactory receptor
neurons (ORN)) in the OE of E11.5 Fgf8 hypomorphs. Second, because FGF8 is important for
developmental cell survival, we examined whether the E11.5 OP in Fgf8 hypomorphs underwent
aberrant levels of apoptosis. Our results showed that Olf-1 immunoreactive (IR) ORNs were
present in the E11.5 OP of wildtype, heterozygous, and homozygous Fgf8 hypomorphs.
Although homozygous Fgf8 hypomorphic embryos possessed a morphologically distinct OP
with normal primary invagination, a secondary recess that presumably gives rise to the
vomeronasal organ and GnRH neurons was reduced or absent. These results indicate that failure
of GnRH neurons to emerge from the OP is not due to global dysgenesis of the OE. Instead,
FGF8 deficiency seems to target the development of the GnRH system with some selectivity.
Furthermore, we found that the Olf-1-IR region of the OP contained very few apoptotic cells,
and there were no gross differences in apoptosis between E11.5 wildtype, heterozygous and
homozygous Fgf8 hypomorphs. Therefore, the altered OP morphology in Fgf8 hypomorphs
cannot be attributed to increased apoptosis at E11.5. Future studies will address if apoptosis prior
to E11.5 contributes to OP abnormality in Fgf8 hypomorphs, and if Fgf8 deficiency leads to
reduced proliferation of the progenitors fated to become GnRH neurons.
Disclosures: W.C. Chung, None; P. Tsai, None.
Poster
278. Sex Differences I
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 278.20/MM13