Deletion of the Ttf1 gene in differentiated neurons disrupts female reproduction without impairing basal ganglia function

Claudio Mastronardi, Gregory G. Smiley, Jacob Raber, Takashi Kusakabe, Akio Kawaguchi, Valerie Matagne, Anja Dietzel, Sabine Heger, Alison E. Mungenast, Ricardo Cabrera, Shioko Kimura, Sergio R. Ojeda

Research output: Contribution to journalArticle

53 Scopus citations

Abstract

Thyroid transcription factor 1 (TTF1) [also known as Nkx2.1 (related to the NK-2 class of homeobox genes) and T/ebp (thyroid-specific enhancer-binding protein)], a homeodomain gene required for basal forebrain morphogenesis, remains expressed in the hypothalamus after birth, suggesting a role in neuroendocrine function. Here,weshow an involvement of TTF1 in the control of mammalian puberty and adult reproductive function. Gene expression profiling of the nonhuman primate hypothalamus revealed that TTF1 expression increases at puberty. Mice in which the Ttf1 gene was ablated from differentiated neurons grew normally and had normal basal ganglia/hypothalamic morphology but exhibited delayed puberty, reduced reproductive capacity, and a short reproductive span. These defects were associated with reduced hypothalamic expression of genes required for sexual development and deregulation of a gene involved in restraining puberty. No extrapyramidal impairments associated with basal ganglia dysfunction were apparent. Thus, although TTF1 appears to fulfill only a morphogenic function in the ventral telencephalon, once this function is satisfied in the hypothalamus, TTF1 remains active as part of the transcriptional machinery controlling female sexual development.

Original languageEnglish (US)
Pages (from-to)13167-13179
Number of pages13
JournalJournal of Neuroscience
Volume26
Issue number51
DOIs
StatePublished - Dec 20 2006

Keywords

  • Basal ganglia
  • Conditional gene deletion
  • Female puberty
  • Homeobox genes
  • Hypothalamus
  • TTF1

ASJC Scopus subject areas

  • Neuroscience(all)

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    Mastronardi, C., Smiley, G. G., Raber, J., Kusakabe, T., Kawaguchi, A., Matagne, V., Dietzel, A., Heger, S., Mungenast, A. E., Cabrera, R., Kimura, S., & Ojeda, S. R. (2006). Deletion of the Ttf1 gene in differentiated neurons disrupts female reproduction without impairing basal ganglia function. Journal of Neuroscience, 26(51), 13167-13179. https://doi.org/10.1523/JNEUROSCI.4238-06.2006