Biomedical subjects

E Annerwall

Publications and source records attributed to E Annerwall.

3 recordsLinked to original sources

PubMed1996

Nuclear import of cellular retinoic acid-binding protein type I in mouse embryonic cells.

Using confocal microscopy we show that cellular retinoic acid-binding protein type I (CRABP I), expressed in several embryonic cell types, displays a compartmentalized subcellular distribution. The protein was excluded from the nucleus in some cells, while in others it accumulated in the nucleus. In the rat cerebellar cell line ST15A, which expresses CRABP I, the protein was found in the cytoplasm with a prominent nuclear exclusion. Addition of retinoic acid to embryos in vivo and to ST15 A cells in vitro did not affect the localization of the protein. Localization of CRABP I and CRABP I fused to a nuclear localization signal expressed in transfected cells, suggested that cell-specific factors may regulate nuclear import of CRABP I. The potential role of a CRABP I-controlled nuclear import of retinoic acid is discussed.

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PubMed1990

Localization of specific retinoid-binding sites and expression of cellular retinoic-acid-binding protein (CRABP) in the early mouse embryo.

Retinoids (vitamin A derivatives) are important for normal embryogenesis and retinoic acid, an acidic derivative of vitamin A, was recently proposed to be an endogenous morphogen. Several retinoids are also potent teratogens. Using an autoradiographic technique, we have identified tissues and cells in early mouse embryos that are able to specifically accumulate a radiolabelled synthetic derivative of retinoic acid. Strong accumulation of radioactivity was seen in several neural crest derivatives and in specific areas of the CNS. Gel filtration analyses of cytosols from embryos that received the radiolabelled retinoid in utero suggested that cellular retinoic acid-binding protein (CRABP) was involved in the accumulation mechanism. Immunohistochemical localization confirmed that cells accumulating retinoids also expressed CRABP. Strong CRABP immunoreactivity was found in neural crest-derived mesenchyme of the craniofacial area, in visceral arches, in dorsal root ganglia and in cells along the gut and the major vessels of the trunk region. In CNS, CRABP expression and retinoid binding was largely restricted to the hindbrain, to a single layer of cells in the roof of the midbrain and to cells in the mantle layer of the neural tube. Our data suggest that cells in the embryo expressing CRABP are target cells for exogenous retinoids as well as endogenous retinoic acid. Retinoic acid may thus play an essential role in normal development of the CNS and of tissues derived from the neural crest. We propose that the teratogenic effects of exogenous retinoids are due to an interference with mechanisms by which endogenous retinoic acid regulates differentiation and pattern formation in these tissues.

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PubMedDate not supplied

Retinoid-binding proteins in craniofacial development.

Cephalic neural crest cells are known to form the frontonasal mesenchyme and contribute to the mesenchyme of the visceral arches. Retinoids affect neural crest cells and their derivatives during development, and thus cause craniofacial, thymus, and conotruncal heart malformations. In addition, retinoids induce malformations of the central nervous system (CNS). Retinoic acid (RA) and its congeners accumulate in a saturable manner in neural crest and neural crest-derived cells, in the hindbrain, and the spinal cord of mouse embryos. Cellular retinoic acid-binding protein (CRABP) was localized by immunohistochemistry in the same areas as were the labelled RA congeners. Thus, CRABP and RA congeners were found in the transitional zone between surface ectoderm and neuropeithelium, from where neural crest cells are known to emanate (day 8 1/2). Later, specific labelling was found in the frontonasal mesenchyme and in the visceral arches. Also in the trunk, neural crest cells were labelled. In CNS, strong staining was seen in the rhombomeres (especially numbers 4-6) of the hindbrain and in the spinal cord. Retinol and cellular retinol-binding protein (CRBP) were more evenly distributed, with exception of surface ectoderm, epithelium of gut, and myocardium, where CRBP was specifically expressed. These findings are discussed in relation to the differential expression of nuclear RA receptors and homeobox genes in the craniofacial region and in the hindbrain. It is possible that RA is important for the normal pattern formation in these regions and acts as a morphogen as previously proposed in limb development.

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