Hedgehog pathway activation alters ciliary signaling in primary hypothalamic cultures

Ruchi Bansal, Staci E. Engle, Patrick J. Antonellis, Logan S. Whitehouse, Anthony J. Baucum, Theodore Cummins, Jeremy F. Reiter, Nicolas F. Berbari

Research output: Contribution to journalArticle

Abstract

Primary cilia dysfunction has been associated with hyperphagia and obesity in both ciliopathy patients and mouse models of cilia perturbation. Neurons throughout the brain possess these solitary cellular appendages, including in the feeding centers of the hypothalamus. Several cell biology questions associated with primary neuronal cilia signaling are challenging to address in vivo. Here we utilize primary hypothalamic neuronal cultures to study ciliary signaling in relevant cell types. Importantly, these cultures contain neuronal populations critical for appetite and satiety such as pro-opiomelanocortin (POMC) and agouti related peptide (AgRP) expressing neurons and are thus useful for studying signaling involved in feeding behavior. Correspondingly, these cultured neurons also display electrophysiological activity and respond to both local and peripheral signals that act on the hypothalamus to influence feeding behaviors, such as leptin and melanin concentrating hormone (MCH). Interestingly, we found that cilia mediated hedgehog signaling, generally associated with developmental processes, can influence ciliary GPCR signaling (Mchr1) in terminally differentiated neurons. Specifically, pharmacological activation of the hedgehog-signaling pathway using the smoothened agonist, SAG, attenuated the ability of neurons to respond to ligands (MCH) of ciliary GPCRs. Understanding how the hedgehog pathway influences cilia GPCR signaling in terminally differentiated neurons could reveal the molecular mechanisms associated with clinical features of ciliopathies, such as hyperphagia-associated obesity.

Original languageEnglish (US)
Article number266
JournalFrontiers in Cellular Neuroscience
Volume13
DOIs
StatePublished - May 14 2019

Fingerprint

Hedgehogs
Cilia
Neurons
Hyperphagia
Feeding Behavior
Hypothalamus
Obesity
Pro-Opiomelanocortin
Aptitude
Appetite
Leptin
Cell Biology
Pharmacology
Ligands
Peptides
Brain
Population

Keywords

  • Cilia
  • Hedgehog signaling
  • Hypothalamus
  • Leptin
  • Melanin concentrating hormone receptor 1
  • Primary neuronal cultures
  • SAG
  • Smoothened

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

Cite this

Bansal, R., Engle, S. E., Antonellis, P. J., Whitehouse, L. S., Baucum, A. J., Cummins, T., ... Berbari, N. F. (2019). Hedgehog pathway activation alters ciliary signaling in primary hypothalamic cultures. Frontiers in Cellular Neuroscience, 13, [266]. https://doi.org/10.3389/fncel.2019.00266

Hedgehog pathway activation alters ciliary signaling in primary hypothalamic cultures. / Bansal, Ruchi; Engle, Staci E.; Antonellis, Patrick J.; Whitehouse, Logan S.; Baucum, Anthony J.; Cummins, Theodore; Reiter, Jeremy F.; Berbari, Nicolas F.

In: Frontiers in Cellular Neuroscience, Vol. 13, 266, 14.05.2019.

Research output: Contribution to journalArticle

Bansal, R, Engle, SE, Antonellis, PJ, Whitehouse, LS, Baucum, AJ, Cummins, T, Reiter, JF & Berbari, NF 2019, 'Hedgehog pathway activation alters ciliary signaling in primary hypothalamic cultures', Frontiers in Cellular Neuroscience, vol. 13, 266. https://doi.org/10.3389/fncel.2019.00266
Bansal, Ruchi ; Engle, Staci E. ; Antonellis, Patrick J. ; Whitehouse, Logan S. ; Baucum, Anthony J. ; Cummins, Theodore ; Reiter, Jeremy F. ; Berbari, Nicolas F. / Hedgehog pathway activation alters ciliary signaling in primary hypothalamic cultures. In: Frontiers in Cellular Neuroscience. 2019 ; Vol. 13.
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