RARβ regulates neuronal cell death and differentiation in the avian ciliary ganglion

Dev Neurobiol. 2015 Nov;75(11):1204-18. doi: 10.1002/dneu.22278. Epub 2015 Jun 12.

Abstract

Programmed cell death during chicken ciliary ganglion (CG) development is mostly discussed as an extrinsically regulated process, guided either by the establishment of a functional balance between preganglionic and postganglionic activity or the availability of target-derived neurotrophic factors. We found that the expression of the gene coding for the nuclear retinoic acid receptor β (RARB) is transiently upregulated prior to and during the execution phase of cell death in the CG. Using retroviral vectors, the expression of RARB was knocked down during embryonic development in ovo. The knockdown led to a significant increase in CG neuron number after the cell death phase. BrdU injections and active caspase-3 staining revealed that this increase in neuron number was due to an inhibition of apoptosis during the normal cell death phase. Furthermore, apoptotic neuron numbers were significantly increased at a stage when cell death is normally completed. While the cholinergic phenotype of the neurons remained unchanged after RARB knockdown, the expression of the proneural gene Cash1 was increased, but somatostatin-like immunoreactivity, a hallmark of the mature choroid neuron population, was decreased. Taken together, these results point toward a delay in neuronal differentiation as well as cell death. The availability of nuclear retinoic acid receptor β (RARβ) and RARβ-induced transcription of genes could therefore be a new intrinsic cue for the maturation of CG neurons and their predisposition to undergo cell death.

Keywords: RARβ; ciliary ganglion; neuronal development; programmed cell death; retinoic acid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Avian Proteins / metabolism*
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Caspase 3 / metabolism
  • Cell Death / physiology
  • Cells, Cultured
  • Chick Embryo
  • Choline O-Acetyltransferase / metabolism
  • Ganglia, Parasympathetic / embryology*
  • Ganglia, Parasympathetic / physiology*
  • LIM-Homeodomain Proteins / metabolism
  • Neurogenesis / physiology*
  • Receptors, Retinoic Acid / genetics
  • Receptors, Retinoic Acid / metabolism*
  • Transcription Factors / metabolism

Substances

  • Avian Proteins
  • Basic Helix-Loop-Helix Transcription Factors
  • CASH-1 protein, Gallus gallus
  • LIM-Homeodomain Proteins
  • Receptors, Retinoic Acid
  • Transcription Factors
  • insulin gene enhancer binding protein Isl-1
  • retinoic acid receptor beta
  • Choline O-Acetyltransferase
  • Caspase 3