Vitamin A Deficiency Results in the Dose-Dependent Acquisition of Anterior Character and Shortening of the Caudal Hindbrain of the Rat Embryo

Vitamin A Deficiency Results in the Dose-Dependent Acquisition of Anterior Character and... The developing nervous system is particularly vulnerable to vitamin A deficiency. Retinoid has been proposed to be a posteriorizing factor during hindbrain development, although direct evidence in the mammalian embryo is lacking. In the present study, pregnant vitamin A-deficient (VAD) rats were fed purified diets containing varying levels of all- trans -retinoic acid (atRA; 0, 0.5, 1.5, 6, 12, 25, 50, 125, or 250 μg/g diet) or were supplemented with retinol. Hindbrain development was studied from embryonic day 10 to 12.5 (∼6 to 40 somites). Normal morphogenesis was observed in all embryos from groups fed 250 μg atRA/g diet or retinol. The most caudal region of the hindbrain was the most sensitive to retinoid insufficiency, as evidenced by a loss of the hypoglossal nerve (cranial nerve XII) in embryos from the 125 μg atRA/g diet group. Further reduction of atRA to 50 μg/g diet led to the loss of cranial nerves IX, X, XI, and XII and associated sensory ganglia IX and X in all embryos as well as the loss of hindbrain segmentation caudal to the rhombomere (r) 3/4 border in a subset of embryos. Dysmorphic orthotopic otic vesicles or immature otic-like vesicles in both orthotopic and caudally ectopic locations were also observed. As the level of atRA was reduced, a loss of caudal hindbrain segmentation was observed in all embryos and the incidence of otic vesicle abnormalities increased. Perturbations in hindbrain segmentation, cranial nerve formation, and otic vesicle development were associated with abnormal patterning of the posterior hindbrain. Embryos from VAD dams fed between 0.5 and 50 μg atRA/g diet exhibited Hoxb-1 protein expression along the entire neural tube caudal to the r3/r4 border at a time when it should be restricted to r4. Krox-20 protein expression was expanded in r3 but absent or reduced in presumptive r5. Hoxd-4 mRNA expression was absent in the posterior hindbrain, and the rostral limit of Hoxb-5 protein expression in the neural tube was anteriorized, suggesting that the most posterior hindbrain region (r7/r8) had been deleted and/or improperly patterned. Thus, when limiting amounts of atRA are provided to VAD dams, the caudal portion of the hindbrain is shortened and possesses r4/r5-like characteristics, with this region finally exhibiting r4-like gene expression when retinoid is restricted even more severely. Thus, regions of the anterior hindbrain (i.e., r3 and r4) appear to be greatly expanded, whereas the posterior hindbrain (r5–r8) is reduced or absent. This work shows that retinoid plays a critical role in patterning, segmentation, and neurogenesis of the caudal hindbrain and serves as an essential posteriorizing signal for this region of the central nervous system in the mammal. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Developmental Biology Elsevier

Vitamin A Deficiency Results in the Dose-Dependent Acquisition of Anterior Character and Shortening of the Caudal Hindbrain of the Rat Embryo

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Publisher
Elsevier
Copyright
Copyright © 2000 Academic Press
ISSN
0012-1606
eISSN
1095-564X
D.O.I.
10.1006/dbio.2000.9635
Publisher site
See Article on Publisher Site

Abstract

The developing nervous system is particularly vulnerable to vitamin A deficiency. Retinoid has been proposed to be a posteriorizing factor during hindbrain development, although direct evidence in the mammalian embryo is lacking. In the present study, pregnant vitamin A-deficient (VAD) rats were fed purified diets containing varying levels of all- trans -retinoic acid (atRA; 0, 0.5, 1.5, 6, 12, 25, 50, 125, or 250 μg/g diet) or were supplemented with retinol. Hindbrain development was studied from embryonic day 10 to 12.5 (∼6 to 40 somites). Normal morphogenesis was observed in all embryos from groups fed 250 μg atRA/g diet or retinol. The most caudal region of the hindbrain was the most sensitive to retinoid insufficiency, as evidenced by a loss of the hypoglossal nerve (cranial nerve XII) in embryos from the 125 μg atRA/g diet group. Further reduction of atRA to 50 μg/g diet led to the loss of cranial nerves IX, X, XI, and XII and associated sensory ganglia IX and X in all embryos as well as the loss of hindbrain segmentation caudal to the rhombomere (r) 3/4 border in a subset of embryos. Dysmorphic orthotopic otic vesicles or immature otic-like vesicles in both orthotopic and caudally ectopic locations were also observed. As the level of atRA was reduced, a loss of caudal hindbrain segmentation was observed in all embryos and the incidence of otic vesicle abnormalities increased. Perturbations in hindbrain segmentation, cranial nerve formation, and otic vesicle development were associated with abnormal patterning of the posterior hindbrain. Embryos from VAD dams fed between 0.5 and 50 μg atRA/g diet exhibited Hoxb-1 protein expression along the entire neural tube caudal to the r3/r4 border at a time when it should be restricted to r4. Krox-20 protein expression was expanded in r3 but absent or reduced in presumptive r5. Hoxd-4 mRNA expression was absent in the posterior hindbrain, and the rostral limit of Hoxb-5 protein expression in the neural tube was anteriorized, suggesting that the most posterior hindbrain region (r7/r8) had been deleted and/or improperly patterned. Thus, when limiting amounts of atRA are provided to VAD dams, the caudal portion of the hindbrain is shortened and possesses r4/r5-like characteristics, with this region finally exhibiting r4-like gene expression when retinoid is restricted even more severely. Thus, regions of the anterior hindbrain (i.e., r3 and r4) appear to be greatly expanded, whereas the posterior hindbrain (r5–r8) is reduced or absent. This work shows that retinoid plays a critical role in patterning, segmentation, and neurogenesis of the caudal hindbrain and serves as an essential posteriorizing signal for this region of the central nervous system in the mammal.

Journal

Developmental BiologyElsevier

Published: Apr 15, 2000

References

  • The development of the neural folds and cranial ganglia of the rat
    Adelmann, H.B.
  • Retinoid signalling and axial patterning during early vertebrate embryogenesis
    Durston, A.J.; van der Wees, J.; Pijnappel, W.W.M.; Schilthius, J.G.; Godsave, S.F.
  • Xenopus hindbrain patterning requires retinoid signaling
    Kolm, P.J.; Apekin, V.; Sive, H.
  • Vitamin A-deficient quail embryos have half a hindbrain and other neural defects
    Maden, M.; Gale, E.; Kostetskii, I.; Zile, M.
  • The role of FGF-3 in early inner ear development: An analysis in normal and kreisler mutant mice
    McKay, I.J.; Lewis, J.; Lumsden, A.
  • Simultaneous determination of endogenous retinoic acid isomers and retinol in human plasma by isocratic normal-phase HPLC with ultraviolet detection
    Meyer, E.; Lambert, W.E.; De Leenheer, A.P.
  • Ectodermal patterning in vertebrate embryos
    Sasai, Y.; De Robertis, E.M.
  • The development and distribution of the cranial neural crest in the rat embryo
    Tan, S.S.; Morriss-Kay, G.

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