TY - JOUR
T1 - NELF is a nuclear protein involved in hypothalamic GnRH neuronal migration
AU - Xu, Ning
AU - Bhagavath, Balasubramanian
AU - Kim, Hyung Goo
AU - Halvorson, Lisa
AU - Podolsky, Robert S.
AU - Chorich, Lynn P.
AU - Prasad, Puttur
AU - Xiong, Wen Cheng
AU - Cameron, Richard S.
AU - Layman, Lawrence C.
PY - 2010/5/5
Y1 - 2010/5/5
N2 - Nasal embryonic LHRH factor (NELF) has been hypothesized to participate in the migration of GnRH and olfactory neurons into the forebrain, a prerequisite for normal hypothalamic-pituitary-gonadal function in puberty and reproduction. However, the biological functions of NELF, which has no homology to any human protein, remain largely elusive. Although mRNA expression did not differ, NELF protein expression was greater in migratory than postmigratory GnRH neurons. Pituitary Nelf mRNA expression was also observed and increased 3-fold after exogenous GnRH administration. Contrary to a previous report, NELF displayed predominant nuclear localization in GnRH neurons, confirmed by mutagenesis of a putative nuclear localization signal resulting in impaired nuclear expression. NELF knockdown impaired GnRH neuronal migration of NLT cells in vitro. These findings and the identification of two putative zinc fingers suggest that NELF could be a transcription factor. Collectively, our findings implicate NELF as a nuclear protein involved in the developmental function of the reproductive axis.
AB - Nasal embryonic LHRH factor (NELF) has been hypothesized to participate in the migration of GnRH and olfactory neurons into the forebrain, a prerequisite for normal hypothalamic-pituitary-gonadal function in puberty and reproduction. However, the biological functions of NELF, which has no homology to any human protein, remain largely elusive. Although mRNA expression did not differ, NELF protein expression was greater in migratory than postmigratory GnRH neurons. Pituitary Nelf mRNA expression was also observed and increased 3-fold after exogenous GnRH administration. Contrary to a previous report, NELF displayed predominant nuclear localization in GnRH neurons, confirmed by mutagenesis of a putative nuclear localization signal resulting in impaired nuclear expression. NELF knockdown impaired GnRH neuronal migration of NLT cells in vitro. These findings and the identification of two putative zinc fingers suggest that NELF could be a transcription factor. Collectively, our findings implicate NELF as a nuclear protein involved in the developmental function of the reproductive axis.
KW - GnRH neuron migration
KW - Hypogonadotropic hypogonadism
KW - Kallmann syndrome
KW - NELF
KW - Nasal embryonic LHRH factor
UR - http://www.scopus.com/inward/record.url?scp=77549086196&partnerID=8YFLogxK
U2 - 10.1016/j.mce.2009.11.016
DO - 10.1016/j.mce.2009.11.016
M3 - Article
C2 - 20025934
AN - SCOPUS:77549086196
SN - 0303-7207
VL - 319
SP - 47
EP - 55
JO - Molecular and Cellular Endocrinology
JF - Molecular and Cellular Endocrinology
IS - 1-2
ER -