Too much of a good thing

retinoic acid as an endogenous regulator of neural differentiation and exogenous teratogen

P J McCaffery, J Adams, M Maden, E Rosa-Molinar

Research output: Contribution to journalArticle

142 Citations (Scopus)

Abstract

Retinoic acid (RA) is essential for both embryonic and adult growth, activating gene transcription via specific nuclear receptors. It is generated, via a retinaldehyde intermediate, from retinol (vitamin A). RA levels require precise regulation by controlled synthesis and catabolism, and when RA concentrations deviate from normal, in either direction, abnormal growth and development occurs. This review describes: (i) how the pattern of RA metabolic enzymes controls the actions of RA; and (ii) the type of abnormalities that result when this pattern breaks down. Examples are given of RA control of the anterior/posterior axis of the hindbrain, the dorsal/ventral axis of the spinal cord, as well as certain sex-specific segments of the spinal cord, using varied animal models including mouse, quail and mosquitofish. These functions are highly sensitive to abnormal changes in RA concentration. In rodents, the control of neural patterning and differentiation are disrupted when RA concentrations are lowered, whereas inappropriately high concentrations of RA result in abnormal development of cerebellum and hindbrain nuclei. The latter parallels the malformations seen in the human embryo exposed to RA due to treatment of the mother with the acne drug Accutane (13-cis RA) and, in cases where the child survives beyond birth, a particular set of behavioural anomalies can be described. Even the adult brain may be susceptible to an imbalance of RA, particularly the hippocampus. This report shows how the properties of RA as a neural induction agent and organizer of segmentation can explain the consequences of RA depletion and overexpression.
Original languageEnglish
Pages (from-to)457-472
Number of pages16
JournalEuropean Journal of Neuroscience
Volume18
Issue number3
Early online date11 Aug 2003
DOIs
Publication statusPublished - Aug 2003

Keywords

  • animals
  • brain
  • cell differentiation
  • embryonic and fetal development
  • humans
  • nervous system physiological phenomena
  • neurons
  • sex characteristics
  • teratogens
  • tretinoin
  • vitamin A
  • vitamin A Deficiency
  • accutane
  • behaviour
  • Gambusia affinis affinis
  • mouse
  • quail
  • central-nervous-system
  • short-chain dehydrogenases/reductases
  • meningeal cells
  • spinal-cord
  • 13-CIS-retinoic acid
  • binding proteins
  • cerebraller development
  • Westerm mosquito ofish

Cite this

Too much of a good thing : retinoic acid as an endogenous regulator of neural differentiation and exogenous teratogen. / McCaffery, P J; Adams, J; Maden, M; Rosa-Molinar, E.

In: European Journal of Neuroscience, Vol. 18, No. 3, 08.2003, p. 457-472.

Research output: Contribution to journalArticle

@article{b6fc6df0b1b24ce49eb81db1a1403185,
title = "Too much of a good thing: retinoic acid as an endogenous regulator of neural differentiation and exogenous teratogen",
abstract = "Retinoic acid (RA) is essential for both embryonic and adult growth, activating gene transcription via specific nuclear receptors. It is generated, via a retinaldehyde intermediate, from retinol (vitamin A). RA levels require precise regulation by controlled synthesis and catabolism, and when RA concentrations deviate from normal, in either direction, abnormal growth and development occurs. This review describes: (i) how the pattern of RA metabolic enzymes controls the actions of RA; and (ii) the type of abnormalities that result when this pattern breaks down. Examples are given of RA control of the anterior/posterior axis of the hindbrain, the dorsal/ventral axis of the spinal cord, as well as certain sex-specific segments of the spinal cord, using varied animal models including mouse, quail and mosquitofish. These functions are highly sensitive to abnormal changes in RA concentration. In rodents, the control of neural patterning and differentiation are disrupted when RA concentrations are lowered, whereas inappropriately high concentrations of RA result in abnormal development of cerebellum and hindbrain nuclei. The latter parallels the malformations seen in the human embryo exposed to RA due to treatment of the mother with the acne drug Accutane (13-cis RA) and, in cases where the child survives beyond birth, a particular set of behavioural anomalies can be described. Even the adult brain may be susceptible to an imbalance of RA, particularly the hippocampus. This report shows how the properties of RA as a neural induction agent and organizer of segmentation can explain the consequences of RA depletion and overexpression.",
keywords = "animals, brain, cell differentiation, embryonic and fetal development, humans, nervous system physiological phenomena, neurons, sex characteristics, teratogens, tretinoin, vitamin A, vitamin A Deficiency, accutane , behaviour, Gambusia affinis affinis , mouse, quail, central-nervous-system, short-chain dehydrogenases/reductases, meningeal cells, spinal-cord, 13-CIS-retinoic acid, binding proteins, cerebraller development, Westerm mosquito ofish",
author = "McCaffery, {P J} and J Adams and M Maden and E Rosa-Molinar",
year = "2003",
month = "8",
doi = "10.1046/j.1460-9568.2003.02765.x",
language = "English",
volume = "18",
pages = "457--472",
journal = "European Journal of Neuroscience",
issn = "0953-816X",
publisher = "Wiley-Blackwell",
number = "3",

}

TY - JOUR

T1 - Too much of a good thing

T2 - retinoic acid as an endogenous regulator of neural differentiation and exogenous teratogen

AU - McCaffery, P J

AU - Adams, J

AU - Maden, M

AU - Rosa-Molinar, E

PY - 2003/8

Y1 - 2003/8

N2 - Retinoic acid (RA) is essential for both embryonic and adult growth, activating gene transcription via specific nuclear receptors. It is generated, via a retinaldehyde intermediate, from retinol (vitamin A). RA levels require precise regulation by controlled synthesis and catabolism, and when RA concentrations deviate from normal, in either direction, abnormal growth and development occurs. This review describes: (i) how the pattern of RA metabolic enzymes controls the actions of RA; and (ii) the type of abnormalities that result when this pattern breaks down. Examples are given of RA control of the anterior/posterior axis of the hindbrain, the dorsal/ventral axis of the spinal cord, as well as certain sex-specific segments of the spinal cord, using varied animal models including mouse, quail and mosquitofish. These functions are highly sensitive to abnormal changes in RA concentration. In rodents, the control of neural patterning and differentiation are disrupted when RA concentrations are lowered, whereas inappropriately high concentrations of RA result in abnormal development of cerebellum and hindbrain nuclei. The latter parallels the malformations seen in the human embryo exposed to RA due to treatment of the mother with the acne drug Accutane (13-cis RA) and, in cases where the child survives beyond birth, a particular set of behavioural anomalies can be described. Even the adult brain may be susceptible to an imbalance of RA, particularly the hippocampus. This report shows how the properties of RA as a neural induction agent and organizer of segmentation can explain the consequences of RA depletion and overexpression.

AB - Retinoic acid (RA) is essential for both embryonic and adult growth, activating gene transcription via specific nuclear receptors. It is generated, via a retinaldehyde intermediate, from retinol (vitamin A). RA levels require precise regulation by controlled synthesis and catabolism, and when RA concentrations deviate from normal, in either direction, abnormal growth and development occurs. This review describes: (i) how the pattern of RA metabolic enzymes controls the actions of RA; and (ii) the type of abnormalities that result when this pattern breaks down. Examples are given of RA control of the anterior/posterior axis of the hindbrain, the dorsal/ventral axis of the spinal cord, as well as certain sex-specific segments of the spinal cord, using varied animal models including mouse, quail and mosquitofish. These functions are highly sensitive to abnormal changes in RA concentration. In rodents, the control of neural patterning and differentiation are disrupted when RA concentrations are lowered, whereas inappropriately high concentrations of RA result in abnormal development of cerebellum and hindbrain nuclei. The latter parallels the malformations seen in the human embryo exposed to RA due to treatment of the mother with the acne drug Accutane (13-cis RA) and, in cases where the child survives beyond birth, a particular set of behavioural anomalies can be described. Even the adult brain may be susceptible to an imbalance of RA, particularly the hippocampus. This report shows how the properties of RA as a neural induction agent and organizer of segmentation can explain the consequences of RA depletion and overexpression.

KW - animals

KW - brain

KW - cell differentiation

KW - embryonic and fetal development

KW - humans

KW - nervous system physiological phenomena

KW - neurons

KW - sex characteristics

KW - teratogens

KW - tretinoin

KW - vitamin A

KW - vitamin A Deficiency

KW - accutane

KW - behaviour

KW - Gambusia affinis affinis

KW - mouse

KW - quail

KW - central-nervous-system

KW - short-chain dehydrogenases/reductases

KW - meningeal cells

KW - spinal-cord

KW - 13-CIS-retinoic acid

KW - binding proteins

KW - cerebraller development

KW - Westerm mosquito ofish

U2 - 10.1046/j.1460-9568.2003.02765.x

DO - 10.1046/j.1460-9568.2003.02765.x

M3 - Article

VL - 18

SP - 457

EP - 472

JO - European Journal of Neuroscience

JF - European Journal of Neuroscience

SN - 0953-816X

IS - 3

ER -