Beyond the neckless phenotype: influence of reduced retinoic acid signaling on motor neuron development in the zebrafish hindbrain

Dev Biol. 2004 Jul 1;271(1):119-29. doi: 10.1016/j.ydbio.2004.03.033.


Retinoic acid (RA) has been identified as a key signal involved in the posteriorization of vertebrate neural ectoderm. The main biosynthetic enzyme responsible for RA signaling in the hindbrain and spinal cord is Raldh2. However, neckless/raldh2-mutant (nls) zebrafish exhibit only mild degrees of anteriorization in the neural ectoderm, compared to full vitamin A deficiency in amniotes and the Raldh2-/- mouse. Here we investigated the role of RA during neuronal development in the zebrafish hindbrain and anterior spinal cord using DEAB, an inhibitor of retinaldehyde dehydrogenases. We show that the nls hindbrain and spinal cord are not fully devoid of RA, since blocking Raldh-mediated RA signaling leads to a more severe hindbrain phenotype than in nls. The anteroposterior distribution of branchiomotor neurons in the facial and more posterior nuclei depends on full RA signaling throughout early and late gastrula stages. In contrast, inhibition of RA synthesis after gastrulation reduces the number of branchiomotor neurons in the vagal nucleus, but has no effect on anteroposterior cell fates. In addition, blockage of RA-mediated signaling not only interferes with the differentiation of branchiomotor neurons and their axons in the hindbrain, but also affects the development of the posterior lateral line nerve.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aldehyde Oxidoreductases / genetics
  • Aldehyde Oxidoreductases / physiology*
  • Animals
  • Immunohistochemistry
  • In Situ Hybridization
  • Morphogenesis
  • Motor Neurons / physiology*
  • Phenotype*
  • Retinal Dehydrogenase
  • Rhombencephalon / embryology*
  • Signal Transduction / physiology*
  • Tretinoin / physiology
  • Zebrafish / embryology*
  • p-Aminoazobenzene / analogs & derivatives*


  • C.I. Solvent Yellow 56
  • Tretinoin
  • p-Aminoazobenzene
  • Aldehyde Oxidoreductases
  • Retinal Dehydrogenase