RT Journal Article
SR Electronic
T1 The Neonatal Ventromedial Hypothalamus Transcriptome Reveals Novel Markers with Spatially Distinct Patterning
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 13624
OP 13634
DO 10.1523/JNEUROSCI.2858-07.2007
VO 27
IS 50
A1 Deborah M. Kurrasch
A1 Clement C. Cheung
A1 Florence Y. Lee
A1 Phu V. Tran
A1 Kenji Hata
A1 Holly A. Ingraham
YR 2007
UL http://www.jneurosci.org/content/27/50/13624.abstract
AB The ventromedial hypothalamus (VMH) is a distinct morphological nucleus involved in feeding, fear, thermoregulation, and sexual activity. It is essentially unknown how VMH circuits underlying these innate responses develop, in part because the VMH remains poorly defined at a cellular and molecular level. Specifically, there is a paucity of cell-type-specific genetic markers with which to identify neuronal subgroups and manipulate development and signaling in vivo. Using gene profiling, we now identify ∼200 genes highly enriched in neonatal (postnatal day 0) mouse VMH tissue. Analyses of these VMH markers by real or virtual (Allen Brain Atlas; http://www.brain-map.org) experiments revealed distinct regional patterning within the newly formed VMH. Top neonatal markers include transcriptional regulators such as Vgll2, SF-1, Sox14, Satb2, Fezf1, Dax1, Nkx2-2, and COUP-TFII, but interestingly, the highest expressed VMH transcript, the transcriptional coregulator Vgll2, is completely absent in older animals. Collective results from zebrafish knockdown experiments and from cellular studies suggest that a subset of these VMH markers will be important for hypothalamic development and will be downstream of SF-1, a critical factor for normal VMH differentiation. We show that at least one VMH marker, the AT-rich binding protein Satb2, was responsive to the loss of leptin signaling (Lepob/ob) at postnatal day 0 but not in the adult, suggesting that some VMH transcriptional programs might be influenced by fetal or early postnatal environments. Our study describing this comprehensive “VMH transcriptome” provides a novel molecular toolkit to probe further the genetic basis of innate neuroendocrine behavioral responses.