The role of retinoid-binding proteins in the generation of pattern in the developing limb, the regenerating limb and the nervous system

Development ◽  
1989 ◽  
Vol 107 (Supplement) ◽  
pp. 109-119 ◽  
Author(s):  
M. Maden ◽  
D. E. Ong ◽  
D. Summerbell ◽  
F. Chytil
Keyword(s):  
Nervous System ◽  
Retinoic Acid ◽  
Chick Embryo ◽  
Neural Tube ◽  
Floor Plate ◽  
Limb Bud ◽  
Commissural Axons ◽  
New Information ◽  
Mantle Layer ◽  
Developing Nervous System

We summarise existing data and describe new information on the levels and distribution of cellular retinoic acid-binding protein (CRABP) and cellular retinolbinding protein (CRBP) in the regenerating axolotl limb, the developing chick limb bud and the nervous system of the chick embryo in the light of the known morphogenetic effects of retinoids on these systems. In the regenerating limb, levels of CRABP rise 3- to 4-fold during regeneration, peaking at the time when retinoic acid (RA) is most effective at causing pattern duplications. The levels of CRBP are low. The potency of various retinoids in causing pattern respecification correlates well with the ability of these compounds to bind to CRABP. In the chick limb bud, the levels of CRABP are high and the levels of CRBP are low. Again the binding of various retinoids to CRABP correlates well with their ability to cause pattern duplications. By immunocytochemistry, we show that CRABP is present at high levels in the progress zone of the limb bud and is distributed across the anteroposterior axis in a gradient with the high point at the anterior margin. In the chick embryo, CRABP levels are high and CRBP levels are low. By immunocytochemistry, CRABP is localised primarily to the developing nervous system, labelling cells and axons in the mantle layer of the neural tube. These become the neurons of the commissural system. Also sensory axons label intensely with CRABP whereas motor axons do not and in the mixed nerves at the brachial plexus sensory and motor components can be distinguished on this basis. In the neural tube, CRBP only stains the ventral floor plate. Since the ventral floor plate may be a source of chemoattractant for commissural axons, we suggest on the basis of these staining patterns that RA may fulfill this role and thus be involved morphogenetically in the developing nervous system.

Development of the central nervous system

2013 ◽  
Author(s):  
Martin E. Atkinson
Keyword(s):  
Spinal Cord ◽  
Nervous System ◽  
Neural Tube ◽  
Large Diameter ◽  
Floor Plate ◽  
Neural Plate ◽  
Ependymal Cells ◽  
High Dose ◽  
Neuronal Processes ◽  
Mantle Layer

The early development of the nervous system, the process of neurulation, has already been outlined in Chapter 8 and illustrated in Figure 8.4. To briefly recap, an area of dorsal ectoderm is induced by the underlying notochord to form the neural plate during the third week of development. The lateral edges of the neural plate rise to form the neural folds which eventually fold over and unite in the midline by the end of the fourth week to produce the neural tube. A distinct cell population on the crest of the neural folds, the neural crest, migrates from the forming neural tube to form various structures, including components of the peripheral nervous system. The closed neural tube consists of a large diameter anterior portion that will become the brain and a longer cylindrical posterior section, the future spinal cord. Initially, the neural plate is a single cell layer, but concentric layers of cells can be recognized by the time the neural tube has closed. An inner layer of ependymal cells surrounds the central spinal canal. Neuroblasts, the precursors of neurons, make up the bulk of the neural tube called the mantle layer; this will become the grey matter of the spinal cord. Neuroblasts do not extend processes until they have completed their differentiation. When the cells in a particular location are fully differentiated, the neuronal processes emerging from the neuroblasts form an outer marginal layer which ultimately becomes the white matter of the spinal cord. Figure 19.1B shows that the neural tube changes shape due to proliferation of cells in the mantle layer. This figure also indicates two midline structures in the roof and floor of the tube, known as the roof plate and floor plate. They are important in the determination of the types of neurons that develop from the mantle layer. The floor plate is induced by the expression of a protein product of a gene called sonic hedgehog (SHH) produced by the underlying notochord; the floor plate then expresses the same gene itself. Neuroblasts nearest to the floor plate receive a high dose of SHH protein and respond by differentiating into motor neurons; as seen in Figure 19.1B, these cells group together to form bilateral ventrolateral basal plates.

The distribution of endogenous retinoic acid in the chick embryo: implications for developmental mechanisms

Development ◽  
1998 ◽  
Vol 125 (21) ◽  
pp. 4133-4144 ◽  
Author(s):  
M. Maden ◽  
E. Sonneveld ◽  
P.T. van der Saag ◽  
E. Gale
Keyword(s):  
Retinoic Acid ◽  
Chick Embryo ◽  
Neural Tube ◽  
Cell System ◽  
Limb Bud ◽  
Lateral Plate ◽  
F9 Cells ◽  
Chick Embryogenesis ◽  
Wide Range ◽  
Very High

The aim of these experiments was to determine the endogenous distribution of retinoic acid (RA) across a wide range of embryonic stages in the chick embryo. By high pressure liquid chromatography, it was revealed that didehydroRA is the most prevalent retinoic acid in the chick embryo and that the tissues of the stage 24 embryo differed widely in their total RA content (didehydroRA + all-trans-RA). Some tissues such as the heart had very little RA and some such as the neural tube had very high levels, the total variation between these two being 29-fold. We showed that these tissues also synthesised RA and released it into the medium, thus validating the use of the F9 reporter cell system for further analyses of younger staged embryos. With these F9 cells, we showed that, at stage 4, the posterior end of the embryo had barely detectably higher levels of RA than the anterior end, but that a significant level of RA generation was detected as soon as somitogenesis began. Then a sharp on/off boundary of RA was present at the level of the first somite. We could find no evidence for a posterior-to-anterior gradient of RA. Throughout further development, various consistent observations were made: the developing brain did not generate RA, but the spinal part of the neural tube generated it at very high levels so there must be a sharp on/off boundary in the region of the hindbrain/spinal cord junction; the mesenchyme surrounding the hindbrain generated RA whereas the hindbrain itself did not; there was a variation in RA levels from the midline outwards with the highest levels of RA in the spinal neural tube followed by lower levels in the somites followed by lower levels in the lateral plate; the posterior half of the limb bud generated higher levels than the anterior half. With these observations, we were able to draw maps of endogenous RA throughout these early stages of chick embryogenesis and the developmental implications of these results are discussed.

Anti-apoptotic role of Sonic hedgehog protein at the early stages of nervous system organogenesis

Development ◽  
2001 ◽  
Vol 128 (20) ◽  
pp. 4011-4020 ◽  
Author(s):  
Jean-Baptiste Charrier ◽  
Françoise Lapointe ◽  
Nicole M. Le Douarin ◽  
Marie-Aimée Teillet
Keyword(s):  
Cell Death ◽  
Nervous System ◽  
Chick Embryo ◽  
Sonic Hedgehog ◽  
Neural Tube ◽  
Primitive Streak ◽  
Embryo Cell ◽  
Floor Plate ◽  
Cell Death Program ◽  
Midline Cells

In vertebrates the neural tube, like most of the embryonic organs, shows discreet areas of programmed cell death at several stages during development. In the chick embryo, cell death is dramatically increased in the developing nervous system and other tissues when the midline cells, notochord and floor plate, are prevented from forming by excision of the axial-paraxial hinge (APH), i.e. caudal Hensen’s node and rostral primitive streak, at the 6-somite stage (Charrier, J. B., Teillet, M.-A., Lapointe, F. and Le Douarin, N. M. (1999). Development126, 4771-4783). In this paper we demonstrate that one day after APH excision, when dramatic apoptosis is already present in the neural tube, the latter can be rescued from death by grafting a notochord or a floor plate fragment in its vicinity. The neural tube can also be recovered by transplanting it into a stage-matched chick embryo having one of these structures. In addition, cells engineered to produce Sonic hedgehog protein (SHH) can mimic the effect of the notochord and floor plate cells in in situ grafts and transplantation experiments. SHH can thus counteract a built-in cell death program and thereby contribute to organ morphogenesis, in particular in the central nervous system.

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.

Expression of a lacZ transgene reveals floor plate cell morphology and macromolecular transfer to commissural axons

Development ◽  
1993 ◽  
Vol 119 (4) ◽  
pp. 1217-1228 ◽  
Author(s):  
R.M. Campbell ◽  
A.C. Peterson
Keyword(s):  
Neural Tube ◽  
Neuronal Cell ◽  
Floor Plate ◽  
Ventral Midline ◽  
Ample Evidence ◽  
Commissural Axons ◽  
Neuronal Cell Bodies ◽  
Lateral Branches ◽  
And Function ◽  
Beta Galactosidase

The floor plate is situated at the ventral midline of the neural tube and is an important intermediate target for commissural axons. During elongation, these axons converge bilaterally on the ventral midline neural tube and after crossing the floor plate make an abrupt rostral turn. Ample evidence indicates that the initial projection of commissural axons to the floor plate is guided by a chemotropic factor secreted by floor plate cells. However, the way in which the subsequent interaction of these axons with the floor plate leads them to make further trajectory changes remains undefined. In an effort to gain further understanding of the structure and function of floor plate cells, we have taken advantage of a line of transgenic mice in which these cells express beta-galactosidase and thus can be stained by histochemical means. In this line, a genomic imprinting mechanism restricts the expression of the lacZ transgene to only a proportion of the floor plate cells, allowing their morphology to be appreciated with particular clarity. Our analysis revealed that the basal processes of floor plate cells are flattened in their rostrocaudal dimension and possess fine lateral branches which are aligned with commissural axons. Unexpectedly, beta-galactosidase activity was also detected within longer transverse linear profiles traversing the floor plate whose ultrastructural appearance was not that of floor plate cells but instead corresponded to that of commissural axons. Enzyme activity was not detected in more proximal axonal segments or in the neuronal cell bodies from which these axons originated. Therefore, we propose that the transgene product, and potentially other proteins synthesized by floor plate cells, can be transferred to decussating axons.

Expression of cellular retinoic acid binding protein in the developing nervous system of mouse embryo

1990 ◽  
Vol 54 (2) ◽  
pp. 161-167 ◽  
Author(s):  
Mariko Momoi ◽  
Takanori Yamagata ◽  
Kou Ichihashi ◽  
Masayoshi Yanagisawa ◽  
Makoto Yamakado ◽  
...  
Keyword(s):  
Nervous System ◽  
Retinoic Acid ◽  
Mouse Embryo ◽  
Binding Protein ◽  
Acid Binding Protein ◽  
Developing Nervous System

The L5 epitope: an early marker for neural induction in the chick embryo and its involvement in inductive interactions

Development ◽  
1991 ◽  
Vol 112 (4) ◽  
pp. 959-970 ◽  
Author(s):  
C. Roberts ◽  
N. Platt ◽  
A. Streit ◽  
M. Schachner ◽  
C.D. Stern
Keyword(s):  
Nervous System ◽  
Chick Embryo ◽  
Neural Induction ◽  
Primitive Streak ◽  
Hybridoma Cells ◽  
Minor Components ◽  
Lower Molecular Mass ◽  
Host Embryo ◽  
Donor Embryo ◽  
Developing Nervous System

The pattern of expression of the carbohydrate epitope L5 was studied during early development of the chick neuroepithelium. Immunoreactivity first appears during gastrulation, at mid-primitive streak stage, and persists until at least 3.5 days of development. The epitope is expressed on all the components of the developing nervous system, both central and peripheral. In immunoblots, the antibody recognises a major component of about Mr 500,000 and several more minor components of lower molecular mass. If a Hensen's node from a donor embryo is transplanted into the area opaca of a host embryo, L5 immunoreactivity appears in the epiblast surrounding the graft. If hybridoma cells secreting the antibody are grafted together with Hensen's node into a host chick embryo, the induction of a supernumerary nervous system is inhibited. We suggest that the L5 epitope is an early and general marker for neural induction and that it may be involved directly in inductive interactions.

Identification of early developing axon projections from spinal interneurons in the chick embryo with a neuron specific beta-tubulin antibody: evidence for a new ‘pioneer’ pathway in the spinal cord

Development ◽  
1990 ◽  
Vol 108 (4) ◽  
pp. 705-716 ◽  
Author(s):  
H. Yaginuma ◽  
T. Shiga ◽  
S. Homma ◽  
R. Ishihara ◽  
R.W. Oppenheim
Keyword(s):  
Spinal Cord ◽  
Chick Embryo ◽  
Neural Tube ◽  
Floor Plate ◽  
C Cells ◽  
Beta Tubulin ◽  
Cell Groups ◽  
Neuronal Processes ◽  
Longitudinal Association ◽  
Chick Spinal Cord

The early development of interneurons in the chick embryo spinal cord was studied using a monoclonal antibody against a neuron-specific beta-tubulin isoform. Early developing interneurons were divided into two cell groups on the basis of their location and the pattern of growth of their axons. One group is composed of cells that establish a primitive longitudinal pathway (PL-cells), whereas the other group contains cells constituting a circumferential pathway (C-cells). The onset of axonal development in both cell groups occurs at stage (st.) 15 (embryonic day, (E), 2) in the branchial segments, which is prior to axonogenesis of motoneurons. PL-cells develop in the region between the floor plate and the motoneuron nucleus. Their axons are the first neuronal processes (‘pioneer axons’) to arrive in the ventrolateral marginal zone and they project both rostrally and caudally to establish a primitive longitudinal association pathway at the ventrolateral surface of the neural tube. This pathway is formed before axons of C-cells arrive in the ventrolateral region. The first C-cells are initially located in the most dorsal portion of the neural tube, whereas later appearing C-cells are also located in both intermediate and ventral regions of the neural tube. The axons of C-cells project ventrally, without fasciculating, along the lateral border of the neural tube. Some of their axons enter the ipsilateral ventrolateral longitudinal pathway at st. 17. We often observed apparent contacts and interactions between preexisting axons of PL-cells and newly arriving axons of C-cells. The axons of commissural C-cells first enter the floor plate at st. 17 and cross the midline at st. 18. Axons of C cells begin to join the contralateral ventrolateral longitudinal pathway at st. 18+ to st. 19. In the floor plate region, contacts between growth cones and axons were often observed. However, axons in the floor plate at these stages were not fasciculated. These observations establish the timing and pattern of growth of axons from two specific populations of early developing interneurons in the chick spinal cord. Additionally, we have identified an early and apparently previously undescribed ‘pioneer’ pathway that constitutes the first longitudinal pathway in the chick spinal cord.

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