TY - JOUR
T1 - Deletion of the Ttf1 gene in differentiated neurons disrupts female reproduction without impairing basal ganglia function
AU - Mastronardi, Claudio
AU - Smiley, Gregory G.
AU - Raber, Jacob
AU - Kusakabe, Takashi
AU - Kawaguchi, Akio
AU - Matagne, Valerie
AU - Dietzel, Anja
AU - Heger, Sabine
AU - Mungenast, Alison E.
AU - Cabrera, Ricardo
AU - Kimura, Shioko
AU - Ojeda, Sergio R.
PY - 2006/12/20
Y1 - 2006/12/20
N2 - 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.
AB - 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.
KW - Basal ganglia
KW - Conditional gene deletion
KW - Female puberty
KW - Homeobox genes
KW - Hypothalamus
KW - TTF1
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UR - http://www.scopus.com/inward/citedby.url?scp=33845766947&partnerID=8YFLogxK
U2 - 10.1523/JNEUROSCI.4238-06.2006
DO - 10.1523/JNEUROSCI.4238-06.2006
M3 - Article
C2 - 17182767
AN - SCOPUS:33845766947
SN - 0270-6474
VL - 26
SP - 13167
EP - 13179
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 51
ER -