Requirement of the orphan nuclear receptor SF-1 in terminal differentiation of ventromedial hypothalamic neurons.
The ventromedial hypothalamic nucleus (VMN) is known to mediate autonomic responses in feeding and reproductive behaviors. To date, the most definitive molecular marker for the VMN is the orphan nuclear receptor steroidogenic factor-1 (SF-1). However, it is unclear whether SF-1 functions in the VMN as it does in peripheral endocrine organ development where loss of SF-1 results in organ agenesis due to apoptosis. Here, we provide evidence that SF-1 has a distinct role in later stages of VMN development by demonstrating the persistence of VMN precursors, the misexpression of an early marker (NKX2-1) concomitant with the absence of a late marker (BDNF neurotrophin), and the complete loss of projections to the bed nucleus of stria terminalis and the amygdala in sf-1 null mice. Our findings demonstrate that SF-1 is required for terminal differentiation of the VMN and suggest that transcriptional targets of SF-1 mediate normal circuitry between the hypothalamus and limbic structures in the telencephalon.
Department of Physiology, University of California, San Francisco, 94143-0444, USA.
Phu V
PV
Tran
Martin B
MB
Lee
Oscar
O
Marín
Baoji
B
Xu
Kevin R
KR
Jones
Louis F
LF
Reichardt
John R
JR
Rubenstein
Holly A
HA
Ingraham
D000679:Amygdala / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000172:deficiency* / Q000235:genetics; D005333:Fetus; D051717:Fushi Tarazu Transcription Factors; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D018398:Homeodomain Proteins; D007150:Immunohistochemistry; D051379:Mice; D018345:Mice, Knockout; D009434:Neural Pathways / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear; D012686:Septal Nuclei / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D054339:Steroidogenic Factor 1; D013687:Telencephalon / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000235:genetics; D014697:Ventromedial Hypothalamic Nucleus / Q000166:cytology / Q000196:embryology* / Q000378:metabolism
D019208:Brain-Derived Neurotrophic Factor; D004268:DNA-Binding Proteins; D051717:Fushi Tarazu Transcription Factors; D018398:Homeodomain Proteins; C000614414:Nkx2-1 protein, mouse; D009687:Nuclear Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D054339:Steroidogenic Factor 1; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors; C515058:steroidogenic factor 1, mouse