Retinoid-binding protein distribution in the developing mammalian nervous system

Development ◽  
1990 ◽  
Vol 109 (1) ◽  
pp. 75-80 ◽  
Author(s):  
M. Maden ◽  
D.E. Ong ◽  
F. Chytil
Keyword(s):  
Nervous System ◽  
Retinoic Acid ◽  
Neural Crest ◽  
Motor Neurons ◽  
Neural Tube ◽  
Binding Protein ◽  
Sympathetic Ganglia ◽  
Retinol Binding Protein ◽  
Otic Vesicle ◽  
Protein Distribution

We have analysed the distribution of cellular retinol-binding protein (CRBP) and cellular retinoic acid-binding protein (CRABP) in the day 8.5-day 12 mouse and rat embryo. CRBP is localised in the heart, gut epithelium, notochord, otic vesicle, sympathetic ganglia, lamina terminalis of the brain, and, most strikingly, in a ventral stripe across the developing neural tube in the future motor neuron region. This immunoreactivity remains in motor neurons and, at later stages, motor axons are labelled in contrast to unlabelled sensory axons. CRABP is localised to the neural crest cells, which are particularly noticeable streaming into the branchial arches. At later stages, neural crest derivatives such as Schwann cells, cells in the gut wall and sympathetic ganglia are immunoreactive. An additional area of CRABP-positive cells are neuroblasts in the mantle layer of the neural tube, which subsequently appear to be the axons and cell bodies of the commissural system. Since retinol and retinoic acid are the endogenous ligands for these binding proteins, we propose that retinoids may play a role in the development and differentiation of the mammalian nervous system and may interact with certain homoeobox genes whose transcripts have also been localised within the nervous system.

Retinoic acid-binding protein, rhombomeres and the neural crest

Development ◽  
1991 ◽  
Vol 111 (1) ◽  
pp. 35-43 ◽  
Author(s):  
M. Maden ◽  
P. Hunt ◽  
U. Eriksson ◽  
A. Kuroiwa ◽  
R. Krumlauf ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Neural Crest ◽  
Neural Tube ◽  
Binding Protein ◽  
Homeobox Genes ◽  
Temporal Distribution ◽  
Stripe Pattern ◽  
Acid Binding Protein ◽  
Branchial Arches ◽  
The Relationship

We have investigated by immunocytochemistry the spatial and temporal distribution of cellular retinoic acid-binding protein (CRABP) in the developing nervous system of the chick embryo in order to answer two specific questions: do neural crest cells contain CRABP and where and when do CRABP-positive neuroblasts first arise in the neural tube? With regard to the neural crest, we have compared CRABP staining with HNK-1 staining (a marker of migrating neural crest) and found that they do indeed co-localise, but cephalic and trunk crest behave slightly differently. In the cephalic region in tissues such as the frontonasal mass and branchial arches, HNK-1 immunoreactivity is intense at early stages, but it disappears as CRABP immunoreactivity appears. Thus the two staining patterns do not overlap, but are complementary. In the trunk, HNK-1 and CRABP stain the same cell populations at the same time, such as those migrating through the anterior halves of the somites. In the neural tube, CRABP-positive neuroblasts first appear in the rhombencephalon just after the neural folds close and then a particular pattern of immunoreactivity appears within the rhombomeres of the hindbrain. Labelled cells are present in the future spinal cord, the posterior rhombencephalon up to rhombomere 6 and in rhombomere 4 thus producing a single stripe pattern. This pattern is dynamic and gradually changes as anterior rhombomeres begin to label. The similarity of this initial pattern to the arrangement of certain homeobox genes in the mouse stimulated us to examine the expression of the chicken Hox-2.9 gene. We show that at stage 15 the pattern of expression of this gene is closely related to that of CRABP. The relationship between retinoic acid, CRABP and homeobox genes is discussed.

The involvement of retinoic acid in the development of the vertebrate central nervous system

Development ◽  
1991 ◽  
Vol 113 (Supplement_2) ◽  
pp. 87-94 ◽  
Author(s):  
Malcolm Maden ◽  
Nigel Holder
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Retinoic Acid ◽  
Vitamin A ◽  
Radial Glia ◽  
Binding Protein ◽  
Retinol Binding Protein ◽  
Published Data ◽  
Vitamin A Derivative ◽  
Vertebrate Central Nervous System

We discuss here both previously published data and our current experiments which suggest that the vitamin A derivative, retinoic acid (RA), may play a role in the development of the vertebrate central nervous system (CNS). This evidence comes from the following: both an excess and a deficiency of vitamin A causes embryonic defects of the CNS; RA has been detected endogenously in the CNS; RA stimulates neurite outgrowth; the retinoic acid receptors have been detected with interesting distributions in the CNS; the binding protein for retinol, namely cellular retinol binding protein (CRBP) is found in the radial glia of the ventral floor plate; the binding protein for RA, namely, cellular retinoic acid binding protein (CRABP) is found in particular sets of axons in the developing spinal cord, in particular rhombomeres in the developing hindbrain and in the neural crest. Some hypotheses for the possible role of RA in various aspects of CNS development are discussed.

The transfer of transthyretin and receptor-binding properties from the plasma retinol-binding protein to the epididymal retinoic acid-binding protein

2002 ◽  
Vol 362 (2) ◽  
pp. 265-271 ◽  
Author(s):  
Manickavasagam SUNDARAM ◽  
Daan M. F. van AALTEN ◽  
John B. C. FINDLAY ◽  
Asipu SIVAPRASADARAO
Keyword(s):  
Retinoic Acid ◽  
Binding Protein ◽  
Binding Pocket ◽  
Retinol Binding Protein ◽  
Cell Surface Receptor ◽  
Acid Binding Protein ◽  
The Family ◽  
Surface Receptor ◽  
A Cell ◽  
Plasma Retinol

Members of the lipocalin superfamily share a common structural fold, but differ from each other with respect to the molecules with which they interact. They all contain eight β-strands (A—H) that fold to form a well-defined β-barrel, which harbours a binding pocket for hydrophobic ligands. These strands are connected by loops that vary in size and structure and make up the closed and open ends of the pocket. In addition to binding ligands, some members of the family interact with other macromolecules, the specificity of which is thought to be associated with the variable loop regions. Here, we have investigated whether the macromolecular-recognition properties can be transferred from one member of the family to another. For this, we chose the prototypical lipocalin, the plasma retinol-binding protein (RBP) and its close structural homologue the epididymal retinoic acid-binding protein (ERABP). RBP exhibits three molecular-recognition properties: it binds to retinol, to transthyretin (TTR) and to a cell-surface receptor. ERABP binds retinoic acid, but whether it interacts with other macromolecules is not known. Here, we show that ERABP does not bind to TTR and the RBP receptor, but when the loops of RBP near the open end of the pocket (L-1, L-2 and L-3, connecting β-strands A—B, C—D and E—F, respectively) were substituted into the corresponding regions of ERABP, the resulting chimaera acquired the ability to bind TTR and the receptor. L-2 and L-3 were found to be the major determinants of the receptor- and TTR-binding specificities respectively. Thus we demonstrate that lipocalins serve as excellent scaffolds for engineering novel biological functions.

Temporally-regulated retinoic acid depletion produces specific neural crest, ocular and nervous system defects

Development ◽  
1997 ◽  
Vol 124 (16) ◽  
pp. 3111-3121 ◽  
Author(s):  
E.D. Dickman ◽  
C. Thaller ◽  
S.M. Smith
Keyword(s):  
Nervous System ◽  
Retinoic Acid ◽  
Neural Crest ◽  
Female Rats ◽  
Retinoid Receptor ◽  
Knock Out ◽  
The Face ◽  
Normal Males ◽  
Temporal Events ◽  
Null Mutant Mice

Both retinoid receptor null mutants and classic nutritional deficiency studies have demonstrated that retinoids are essential for the normal development of diverse embryonic structures (e.g. eye, heart, nervous system, urogenital tract). Detailed analysis of retinoid-modulated events is hampered by several limitations of these models, including that deficiency or null mutation is present throughout gestation, making it difficult to isolate primary effects, and preventing analysis beyond embryolethality. We developed a mammalian model in which retinoid-dependent events are documented during distinct targeted windows of embryogenesis. This was accomplished through the production of vitamin A-depleted (VAD) female rats maintained on sufficient oral retinoic acid (RA) for growth and fertility. After mating to normal males, these RA-sufficient/VAD females were given oral RA doses which allowed for gestation in an RA-sufficient state; embryogenesis proceeded normally until retinoids were withdrawn dietarily to produce a sudden, acute retinoid deficiency during a selected gestational window. In this trial, final RA doses were administered on E11.5, vehicle at E12.5, and embryos analyzed on E13.5; during this 48 hour window, the last RA dose was metabolized and embryos progressed in a retinoid-deficient state. RA-sufficient embryos were normal. Retinoid-depleted embryos exhibited specific malformations of the face, neural crest, eyes, heart, and nervous system. Some defects were phenocopies of those seen in null mutant mice for RXR alpha(−/−), RXR alpha(−/−)/RAR alpha(−/−), and RAR alpha(−/−)/RAR gamma(−/−), confirming that RA transactivation of its nuclear receptors is essential for normal embryogenesis. Other defects were unique to this deficiency model, showing that complete ligand ‘knock-out’ is required to see those retinoid-dependent events previously concealed by receptor functional redundancy, and reinforcing that retinoid receptors have separate yet overlapping contributions in the embryo. This model allows for precise targeting of retinoid form and deficiency to specific developmental windows, and will facilitate studies of distinct temporal events.

Developmental potential of neural crest-derived cells migrating from segments of developing quail bowel back-grafted into younger chick host embryos

Development ◽  
1990 ◽  
Vol 109 (2) ◽  
pp. 411-423 ◽  
Author(s):  
T.P. Rothman ◽  
N.M. Le Douarin ◽  
J.C. Fontaine-Perus ◽  
M.D. Gershon
Keyword(s):  
Neural Crest ◽  
Neural Tube ◽  
Peripheral Nerves ◽  
Sympathetic Ganglia ◽  
Limb Bud ◽  
Pigment Cells ◽  
Developmental Potential ◽  
Migratory Experience ◽  
Host Embryo

The technique of back-transplantation was used to investigate the developmental potential of neural crest-derived cells that have migrated to and colonized the avian bowel. Segments of quail bowel (removed at E4) were grafted between the somites and neural tube of younger (E2) chick host embryos. Grafts were placed at a truncal level, adjacent to somites 14–24. Initial experiments, done in vitro, confirmed that crest-derived cells are capable of migrating out of segments of foregut explanted at E4. The foregut, which at E4 has been colonized by cells derived from the vagal crest, served as the donor tissue. Comparative observations were made following grafts of control tissues, which included hindgut, lung primordia, mesonephros and limb bud. Additional experiments were done with chimeric bowel in which only the crest-derived cells were of quail origin. Targets in the host embryos colonized by crest-derived cells from the foregut grafts included the neural tube, spinal roots and ganglia, peripheral nerves, sympathetic ganglia and the adrenals, but not the gut. Donor cells in these target organs were immunostained by the monoclonal antibody, NC-1, indicating that they were crest-derived and developing along neural or glial lineages. Some of the crest-derived cells (NC-1-immunoreactive) that left the bowel and reached sympathetic ganglia, but not peripheral nerves or dorsal root ganglia, co-expressed tyrosine hydroxylase immunoreactivity, a neural characteristic never expressed by crest-derived cells in the avian gut. None of the cells leaving enteric back-grafts produced pigment. Cells of mesodermal origin were also found to leave donor explants and aggregate in dermis and feather germs near the grafts. These observations indicate that crest-derived cells, having previously migrated to the bowel, retain the ability to migrate to distant sites in a younger embryo. The routes taken by these cells appear to reflect, not their previous migratory experience, but the level of the host embryo into which the graft is placed. Some of the population of crest-derived cells that leave the back-transplanted gut remain capable of expressing phenotypes that they do not express within the bowel in situ, but which are appropriate for the site in the host embryo to which they migrate.

Analysis of the development of the nervous system of the zebrafish, Brachydanio rerio

Development ◽  
1968 ◽  
Vol 19 (2) ◽  
pp. 109-119
Author(s):  
Judith Shulman Weis
Keyword(s):  
Spinal Cord ◽  
Nervous System ◽  
Neural Crest ◽  
Neural Tube ◽  
Sympathetic Neurons ◽  
Dorsal Surface ◽  
Teleost Fishes ◽  
Brachydanio Rerio ◽  
Solid Structure ◽  
Derivatives Of

In teleost fishes, unlike many other vertebrates, the spinal cord originates as a solid structure, the neural keel, which subsequently hollows out. Unlike vertebrates in which the neural tube is formed from neural folds, and where the neural crest arises from wedge-shaped masses of tissue connecting the neural tube to the general ectoderm, teleosts do not possess a clear morphological neural crest. Initially, the dorsal surface of the keel is broadly attached to the ectoderm as described by Shepard (1961). As the neural primordia become larger and more discrete, the region of attachment narrows, and cells become loose (the ‘loose crest stage’). These cells represent the neural crest. Subsequently they begin to migrate and to differentiate into the various derivatives of neural crest. Both sensory and sympathetic neurons arise from neural crest. At the time of their migration the cells are not morphologically distinguishable.

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