PUBLICATION

The neonatal ventromedial hypothalamus transcriptome reveals novel markers with spatially distinct patterning

Authors
Kurrasch, D.M., Cheung, C.C., Lee, F.Y., Tran, P.V., Hata, K., and Ingraham, H.A.
ID
ZDB-PUB-071219-19
Date
2007
Source
The Journal of neuroscience : the official journal of the Society for Neuroscience   27(50): 13624-13634 (Journal)
Registered Authors
Kurrasch, Deborah
Keywords
VMH, SF-1, CNS development, gene profiling, hypothalamus, Vgll2, zebrafish
MeSH Terms
  • Age Factors
  • Animals
  • Animals, Newborn
  • Biomarkers/metabolism
  • Cell Differentiation/genetics
  • Embryo, Nonmammalian
  • Gene Expression Profiling*
  • Gene Expression Regulation, Developmental/genetics*
  • Hypothalamus/cytology
  • Hypothalamus/growth & development
  • Hypothalamus/metabolism*
  • Leptin/metabolism
  • Male
  • Matrix Attachment Region Binding Proteins/genetics
  • Matrix Attachment Region Binding Proteins/metabolism
  • Mice
  • Mice, Mutant Strains
  • Muscle Proteins/genetics
  • RNA, Messenger/metabolism
  • Signal Transduction/genetics
  • Steroidogenic Factor 1/genetics
  • Steroidogenic Factor 1/metabolism
  • Transcription Factors/genetics
  • Transcription Factors/metabolism
  • Zebrafish
PubMed
18077674 Full text @ J. Neurosci.
Abstract
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 approximately 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 (Lep(ob/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.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping