TY - JOUR T1 - A Role for FE65 in Controlling GnRH-1 Neurogenesis JF - The Journal of Neuroscience JO - J. Neurosci. SP - 480 LP - 491 DO - 10.1523/JNEUROSCI.4698-10.2011 VL - 31 IS - 2 AU - Paolo E. Forni AU - Michele Fornaro AU - Suzanne Guénette AU - Susan Wray Y1 - 2011/01/12 UR - http://www.jneurosci.org/content/31/2/480.abstract N2 - Gonadotropin-releasing hormone-1 (GnRH-1) neurons migrate from the nasal placode to the forebrain where they control gonadal function via the hypothalamic–pituitary–gonadal axis. The birth of GnRH-1-expressing neurons is one of the first neurogenic events in the developing nasal placode. By gene expression screening on single GnRH-1 neurons, amyloid precursor binding protein-1 (FE65) was identified in migratory GnRH-1 neurons. FE65 has been shown to modulate β1-integrin dynamics, actin cytoskeleton, cell motility, and FE65/amyloid precursor protein signaling has been described in neuro/glial cell fate determination as well as in modulating neurogenesis. Analysis of two mouse lines, one deficient for the 97 kDa FE65 isoform and a second deficient for the 97 and 60 kDa forms of FE65, showed overlapping phenotypes. In both lines, no migratory defects of the GnRH-1 neurons were observed, but a 25% increase in GnRH-1 neuronal number during embryonic development was found. Bromodeoxyuridine birth tracing and spatiotemporal tracking of GnRH-1 cell precursors demonstrated that the lack of the N-terminal portion of FE65, which includes part of the functional nuclear translocation/gene transcription domain of FE65 (WW domain), extends the timing of GnRH-1 neurogenesis in the developing nasal placode without affecting proliferation of GnRH-1 neuronal progenitors or cell death. The observed changes in the dynamics of GnRH-1 neurogenesis highlight a unique role for the 97 kDa isoform of FE65 and suggest that GnRH-1 cells, which have a short neurogenic window, originate from multipotent progenitors able to generate distinct cell types as GnRH-1 neurogenesis declines in response to environmental changes. ER -