The LIM-homeobox transcription factor Isl1 plays crucial roles in the development of multiple arcuate nucleus neurons

Bora Lee, Seunghee Lee, Soo Kyung Lee, Jae W. Lee

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

Neurons in the hypothalamic arcuate nucleus relay and translate important cues from the periphery into the central nervous system. However, the gene regulatory program directing their development remains poorly understood. Here, we report that the LIM-homeodomain transcription factor Isl1 is expressed in several subpopulations of developing arcuate neurons and plays crucial roles in their fate specification. Mice with conditional deletion of the Isl1 gene in developing hypothalamus display severe deficits in both feeding and linear growth. Consistent with these results, their arcuate nucleus fails to express key fate markers of Isl1-expressing neurons that regulate feeding and growth. These include the orexigenic neuropeptides AgRP and NPY for specifying AgRP-neurons, the anorexigenic neuropeptide αMSH for POMC-neurons, and two growth-stimulatory peptides, growth hormone-releasing hormone (GHRH) for GHRH-neurons and somatostatin (Sst) for Sst-neurons. Finally, we show that Isl1 directly enhances the expression of AgRP by cooperating with the key orexigenic transcription factors glucocorticoid receptor and brain-specific homeobox factor. Our results identify Isl1 as a crucial transcription factor that plays essential roles in the gene regulatory program directing development of multiple arcuate neuronal subpopulations.

Original languageEnglish (US)
Pages (from-to)3763-3773
Number of pages11
JournalDevelopment (Cambridge)
Volume143
Issue number20
DOIs
StatePublished - Oct 15 2016

Keywords

  • Arcuate neurons
  • Bsx
  • GR
  • Hypothalamus
  • Isl1

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

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