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PubMed2004

Benign notochordal cell tumors: A comparative histological study of benign notochordal cell tumors, classic chordomas, and notochordal vestiges of fetal intervertebral discs.

Intraosseous benign notochordal cell tumors are recently recognized conditions that may undergo malignant transformation to classic chordomas. This study attempts to define the morphologic and immunohistochemical characteristics of 34 benign notochordal cell tumors by contrasting them with classic chordomas and the notochordal vestiges in fetal intervertebral discs. Benign notochordal cell tumors were characterized by well-demarcated though unencapsulated sheets of adipocyte-like vacuolated and less vacuolated eosinophilic cells within axial bones. The round nuclei were mildly polymorphic but bland. The tumor cells often contained cytoplasmic eosinophilic hyaline globules and lack any intercellular myxoid matrix or necrosis. The involved bone trabeculae were often sclerotic without evidence of bone destruction. The histologic features were different from those of both notochordal vestiges in fetal intervertebral discs and classic chordomas. There was overlap in immunohistochemical reactivity of benign notochordal cell tumors and chordomas, but notochordal vestiges failed to demonstrate cytokeratin 18 positivity. A more appropriate term for the lesions is "benign notochordal cell tumor" rather than "notochordal rest" or "notochordal hamartoma" as they are not rests and do not fulfill the definition of hamartoma. Benign notochordal cell tumors do not need any surgical procedure and must be adequately recognized to prevent unnecessary operations.

Adult↗

PubMed1995

Mesodermal patterning during avian gastrulation and neurulation: experimental induction of notochord from non-notochordal precursor cells.

The cells that are normally fated to form notochord occupy a region at the rostral tip of the primitive streak at late gastrula/early neurula stages of avian and mammalian development. If these cells are surgically removed from avian embryos in culture, a notochord will nonetheless form in the majority of cases. The origin of this reconstituted notochord previously had not been investigated and was the objective of this study. Chick embryos at late gastrulal early neurula stages were cultured, and the rostral tip of the primitive streak including Hensen's node was removed and replaced with non-node cells from quail epiblast to ensure that the cells normally fated to be notochord would be absent and that healing of the blastoderm would occur. Embryos were allowed to develop for 24 hr, and the presence and origin (host or graft) of the notochord were assessed using antibodies against notochord or quail cells. Two notochords typically developed; both were almost exclusively of host origin. The primitive streak, and in some cases adjacent tissues, was removed from another group of embryos in an attempt to estimate the mediolateral position and extent of the cells required to form reconstituted notochord. Additional experimental embryos with and without grafts were transected at various rostrocaudal levels in an attempt to estimate the rostrocaudal extent of the cells required to form reconstituted notochord. Finally, various levels of the primitive streak either were placed in a neutral environment (the germ cell crescent) or were grafted in place of the node. Collective results from all experiments indicate that the areas lateral to the rostral portion of the primitive streak, estimated to have a rostrocaudal span of less than 500 microns and a mediolateral extent of less than 250 microns, are critical for formation of the reconstituted notochord. Fate mapping and histological examination of this region identify 4 possible precursor cell populations. Further studies are underway to determine which of the 4 possible precursor cell types forms or induces the reconstituted notochord, and which tissue interactions underlie this change in cell fate.

Animals↗

PubMed2003

Sox5 and Sox6 are required for notochord extracellular matrix sheath formation, notochord cell survival and development of the nucleus pulposus of intervertebral discs.

The notochord has major roles in vertebral column formation: indirectly by inducing sclerotome cell differentiation; and directly by forming the nucleus pulposus of intervertebral discs. Sox5 and Sox6 encode Sry-related HMG box transcription factors that act redundantly to promote chondroblast differentiation in all cartilages of the mouse embryo. We show that Sox5 and Sox6 are expressed in the notochord cell lineage and required for notochord late development. In Sox5(-/-)/Sox6(-/-) embryos, the notochord formed a typical rod-like structure. It fulfilled its inductive functions, as indicated by expression of sonic hedgehog and sclerotome specification. However, the notochord failed to become surrounded with an extracellular matrix sheath. This phenotype was associated with a downregulation of extracellular matrix genes, including the genes for collagen 2, aggrecan and perlecan in both notochord cells and surrounding chondrocytic cells of presumptive inner annuli and vertebral bodies. The mutant notochord then underwent an aberrant, fatal dismantling after sclerotome cell migration. Its cells became removed first from intervertebral spaces and then from vertebral bodies, and it progressively underwent apoptosis. Meanwhile, the development of inner annuli and vertebral bodies was dramatically impaired. Consequently, the vertebral column of Sox5(-/-)/Sox6(-/-) fetuses consisted of a very deficient cartilage and was devoid of nuclei pulposi. In Sox5(-/-)/Sox6(+/-) and more severely in Sox5(+/-)/Sox6(-/-) embryos, the notochord sheath was thinner, but cells survived. By birth, nuclei pulposi were rudimentary, and its cells poorly swelled and still expressing sonic hedgehog. Hence, Sox5 and Sox6 are required for notochord extracellular matrix sheath formation, notochord cell survival and formation of nuclei pulposi. Through these roles and essential roles in cartilage formation, they are central transcriptional regulators of vertebral column development.

Animals↗

PubMed2004

Adriamycin induces notochord hypertrophy with conservation of sonic hedgehog expression in abnormal ectopic notochord in the adriamycin rat model.

BACKGROUND/PURPOSE: The Adriamycin rat model (ARM) is a well-established model of the Vertebral, Anorectal, Cardiac, Tracheoesophageal, Renal, Limb (VACTERL) association. The notochord, which expresses Sonic Hedgehog (Shh), has been found to be grossly malformed with ventral ectopic branches in the foregut region of embryos in the ARM. The authors designed this study to test the hypothesis that Shh-expressing ectopic notochord could contribute to an increased volume of notochord relative to total embryo volume, resulting in an increased concentration of Shh in the notochord of affected embryos. METHODS: Adriamycin was administered intraperitoneally to rats on days 7 (E7), E8, and E9 of gestation and saline to control animals. Embryos recovered at E12 and E14 were examined immunohistochemically for Shh expression. Quantitative morphology using the Cavalieri technique was performed to determine embryo and notochord volume. RESULTS: Embryos in both Adriamycin and control groups at E12 and E14 showed comparable levels of Shh expression in notochord at all locations. The percentage of notochord per embryo was significantly increased in Adriamycin embryos at E12 and E14 compared with equivalent controls. CONCLUSIONS: These data suggest that Adriamycin induces notochord hypertrophy. With all regions of the notochord secreting Shh, this could result in a higher concentration gradient of Shh in close abnormal proximity to the foregut, possibly contributing to the malformations found in the VACTERL association.

Abnormalities, Drug-Induced↗

PubMed1993

Altered Pax gene expression in murine notochord mutants: the notochord is required to initiate and maintain ventral identity in the somite.

We have characterised the patterning capacity of the notochord on the somite using the murine Pax-1 gene as a ventral, and Pax-3 as a dorsal molecular marker. As model systems we chose the four mouse notochord mutants Brachyury curtailed (Tc), Danforth's short tail (Sd), Pintail (Pt) and truncate (tc). Their notochord either is initially absent or progressively degenerates. The use of these mutants enabled us to compare the effect of graded notochord deficiencies. All four mutants show premature termination of the vertebral column. This phenotype can be traced back to an impaired dorsoventral specification of the somites. In tc/tc and Tc/+ embryos the notochord in the affected regions is missing from the beginning. Consequently, Pax-1 is never activated, and Pax-3 remains to be expressed in the entire somite. In contrast, in Sd and Pt embryos the notochord secondarily degenerates. At the end of the prevertebral column Pax-1 expression is lost, while the Pax-3 signal occupies the former Pax-1 expressing zone. The altered pax gene expression in the notochord mutants suggests that the notochord is required for two processes in the dorsoventral patterning of the somite: first the induction of ventral structures, and second the maintenance of the ventral fate.

Animals↗

PubMed1995

The developmental relationships of the neural tube and the notochord: short and long term effects of the notochord on the dorsal spinal cord.

Patterning of the ventral half of the neural tube results from the inductive influence of the notochord and of the floor plate. We have studied here the effect of an ectopically grafted notochord on the development of the dorsalmost part of the neural tube i.e. roof plate and alar plates. We show that at their early stages, dorsal genes are repressed by the dorsal graft of a notochord, as shown previously in other studies. We found also that when the notochord is implanted in a mediodorsal position on top of the roof plate (and not laterally as previously performed in other studies) the genes specifics of the floor plate are not induced, and motoneurons do not differentiate. The notochord prevents the formation of the medial septum from roof plate cells and induces their active proliferation between E5 and E7. Roof and dorsal alar plates derived cells start to die from E7 onward leaving a dorsally truncated spinal cord. If the notochord is grafted at 20 degrees-30 degrees from the sagittal plane ventral genes and structures are induced and the roof plate differentiates normally. We conclude that roof plate cells exhibit a specific response to notochord signals, the short range effect of which is thus strikingly demonstrated.

Animals↗

PubMed2006

Immunohistochemical study of cytoskeletal and extracellular matrix components in the notochord and notochordal sheath of amphioxus.

A major cytoskeletal and extracellular matrix proteins of the amphioxus notochordal cells and sheath were detected by immunohistochemical techniques. The three-layered amphioxus notochordal sheath strongly expressed fish collagen type I in its outer and middle layers, while in the innermost layer expression did not occur. The amphioxus notochordal sheath was reactive to applied anti-human antibodies for intermediate filament proteins such as cytokeratins, desmin and vimentin, as well as to microtubule components (beta-tubulin), particularly in the area close to the epipharyngeal groove. Alpha-smooth muscle actin was expressed in some notochordal cells and in the area of the notochordal attachment to the sheath. Thus muscular nature of notochordal cells was shown by immunohistochemistry in tissue section. Our results confirm that genes encoding intermediate filament proteins, microtubules and microfilaments are highly conserved during evolution. Collagen type I was proven to be the key extracellular matrix protein that forms the amphioxus notochordal sheath.

Actin Cytoskeleton↗

PubMed2002

First histologically confirmed case of a classic chordoma arising in a precursor benign notochordal lesion: differential diagnosis of benign and malignant notochordal lesions.

The first histologically confirmed case of a classic chordoma arising in a precursor benign notochordal lesion is presented and the differential diagnosis between benign and malignant notochordal lesions is discussed. A 57-year-old man presented with a classic chordoma in the coccyx. The resected specimen demonstrated a small intraosseous benign notochordal lesion in the coccyx, which was adjacent to the classic chordoma. Also seen were two separate, similar benign lesions in the sacrum. The classic chordoma consisted of multiple lobules that were separated by thin fibrous septa and that showed cords or strands of atypical physaliphorous cells set within an abundant myxoid matrix. In contrast, the benign lesions consisted of intraosseous sheets of bland physaliphorous cells without any extracellular matrix. The affected bone trabeculae showed sclerotic reactions. It was concluded that benign and malignant notochordal lesions can be distinguished microscopically.

Chordoma↗

PubMed1995

Induction of notochord cell intercalation behavior and differentiation by progressive signals in the gastrula of Xenopus laevis.

We show that notochord-inducing signals are present during Xenopus laevis gastrulation and that they are important for both inducing and organizing cell behavior and differentiation in the notochord. Previous work showed that convergent extension of prospective notochordal and somitic mesoderm occurs by mediolateral cell intercalation to produce a longer, narrower tissue. Mediolateral cell intercalation is driven by bipolar, mediolaterally directed protrusive activity that elongates cells and then pulls them between one another along the mediolateral axis. This cell behavior, and subsequent notochordal cell differentiation, begins anteriorly and spreads posteriorly along the notochordal-somitic boundary, and from this lateral boundary progresses medially towards the center of the notochord field. To examine whether these progressions of cell behaviors and differentiation are induced and organized during gastrulation, we grafted labeled cells from the prospective notochordal, somitic and epidermal regions of the gastrula into the notochordal region and monitored their behavior by low light, fluorescence videomicroscopy. Prospective notochordal, epidermal and somitic cells expressed mediolateral cell intercalation behavior in an anterior-to-posterior and lateral-to-medial order established by the host notochord. Behavioral changes were induced first and most dramatically among cells grafted next to the notochordal-somitic boundary, particularly those in direct contact with the boundary, suggesting that the boundary may provide signals that both induce and organize notochordal cell behaviors. By physically impeding normal convergent extension movements, notochordal cell behaviors and differentiation were restricted to the anteriormost notochordal region and to the lateral notochordal-somitic boundary. These results show that mediolateral cell intercalation behavior and notochordal differentiation can be induced in the gastrula stage, among cells not normally expressing these characteristics, and that these characteristics are induced progressively, most likely by signals emanating from the notochordal-somitic boundary. In addition, they show that morphogenetic movements during gastrulation are necessary for complete notochord formation and that the prospective notochord region is not determined by the onset of gastrulation.

Animals↗

PubMed1999

Comparative study of shape, course, and disintegration of the rostral notochord in some vertebrates, especially humans.

The rostral part of the notochord reveals many peculiarities compared with the trunk mesoderm. Furthermore, its role in head formation and inductive processes in the head is not as well understood as the interaction of the trunk notochord with the spinal cord and somites. To interpret experimental and molecular biological examinations in the developing head region, exact knowledge about morphological features of the rostral notochord is fundamental. Here we show that the rostral notochord reveals variations that depend on species and individual. We describe morphological characteristics of the rostral (head) notochord in human embryos (Carnegie stages X-XIV), which are shown in semithin sections and three-dimensional graphic reconstructions. Special attention is paid to the relationship of the notochord with the prechordal mesoderm and the adenohypophysis. We propose that in the human the rostral notochordal tip terminates at Rathke's pouch, whereas in the chick prechordal mesoderm is found in between the notochordal tip and the anlage of the adenohypophysis. The behaviour of the notochord at the end of the embryonic period proper and early fetal time is shown in sagittal histological sections of 16 to 49 mm CRL human embryos. Position and disintegration of the rostral notochord is also described in embryos of cat (8-25 mm), mouse (stage 21-24 according to Theiler) and chicken (stage 22-26 HH). A synopsis reveals the different course of the notochord within, at the inner or outer side of the basioccipital cartilage. The course of rostral notochord is determined by its attachment points at the hypophysis, the pharynx or the footplate of the brain. In all species, it has an undulating course. Its rostral tip is highly coiled, and fragments or splinters are found within the anlage of the dorsum sellae. Thus, we have reasons to believe that the adenohypophysis is a hindrance for the rostral elongation of the notochord. Variable adhesions between notochord and pharyngeal epithelium are considered to be responsible for invaginations of the pharyngeal wall forming bursae pharyngeae. In contrast to other authors, we observed in the mouse that rostrally the notochord bends ventral and penetrates the chondrocranium at the level of the later synchondrosis basisphenoidale to build a bursa pharyngea. Finally, partial duplications of two human notochords are described.

Animals↗

PubMed1996

Basic fibroblast growth factor induces notochord formation and the expression of As-T, a Brachyury homolog, during ascidian embryogenesis.

The tadpole larva of an ascidian develops 40 notochord cells in the center of its tail. Most of the notochord cells originate from the A-line precursors, among which inductive interactions are required for the subsequent differentiation of notochord. The presumptive-endoderm blastomeres or presumptive-notochord blastomeres themselves are inducers of notochord formation. Notochord induction takes place during the 32-cell stage. In amphibia, mesoderm induction is thought to be mediated by several growth factors, for example, activins and basic fibroblast growth factor (bFGF). In the ascidian, Halocynthia roretzi, treatment with bFGF of presumptive-notochord blastomeres that had been isolated at the early 32-cell stage promoted the formation of notochord at a low concentration of bFGF (0.02 ng/ml), while activin failed to induce notochord differentiation. The effect of bFGF reached a maximum at the end of the 32-cell stage and rapidly faded at the beginning of the subsequent cleavage, the time for full induction of notochord being at least 20 minutes. The expression of As-T, a previously isolated ascidian homolog of the mouse Brachyury (T) gene, starts at the 64-cell stage and is detectable exclusively in the presumptive-notochord blastomeres. The present study showed that presumptive-notochord blastomeres, isolated at the early 32-cell stage, neither differentiated into notochord nor expressed the As-T gene. However, when the presumptive-notochord blastomeres were coisolated or recombined with inducer blastomeres, transcripts of As-T were detected. When presumptive-notochord blastomeres were treated with bFGF, the expression of the As-T gene was also detected. These results suggest that inductive interaction is required for the expression of the As-T gene and that the expression of the As-T gene is closely correlated with the determined state of the notochord-precursor cells.

Activins↗

PubMed1988

Development of the notochord in human embryos: ultrastructural, histochemical, and immunohistochemical studies.

In the present study of the notochord, the specimens were 54 externally normal human embryos ranging between Carnegie stages 13 and 23. The following staining procedures were used: periodic acid-Schiff (PAS), modified method of PAS, alcian blue, colloidal iron, and toluidine blue. Routine electron microscopic techniques were used. Immunoreactivity of the notochord to alpha-enolase was also examined. The notochord cells were undifferentiated in stage 13 with few intracellular organelles. The microfibrils and deposition of acid mucopolysaccharides appeared in the notochordal sheath in stage 14. The characteristic relation of mitochondria with rough endoplasmic reticulum was observed. Golgi complexes increased in the perinuclear region in stage 15. The layer of microfibrils in the notochordal sheath initially separated from the notochord in stage 16. Glycogen, mucoprotein, neutral mucopolysaccharides, and glycolipids began to increase in the mesenchymal cells around the notochord, starting at stage 16. Acid mucopolysaccharides increased in the notochordal sheath and in the matrix of the precartilage area around the notochord as this embryonic stage advanced. It was also revealed that the immunoreactivity of the notochord to alpha-enolase remained constant during the embryonic period. The results show that the notochord is transformed from an apparently undifferentiated organ into an organ with secretory activity in stage 14, producing microfibrils and depositing acid mucoplysaccharides in the notochordal sheath. The immunoreactivity of the notochord to alpha- and gamma-enolase isoenzymes and the development of the notochord are discussed. This study was undertaken to provide additional information on the development of tumors of notochordal origin.

Embryo, Mammalian↗

PubMedDate not supplied

Expression of muscle-related genes and two MyoD genes during amphioxus notochord development.

The notochord is one of the diagnostic features of the phylum Chordata. Despite the similarities in the early morphogenetic patterns of the notochords of various chordates, they are strikingly distinct from one another at the histological level. The amphioxus notochord is one example of an evolutionary novelty because it is made up of muscle cells. Our previous expressed sequence tag analysis, targeting messenger RNAs expressed in the adult amphioxus notochord, demonstrated that many muscle-related genes are expressed there. To characterize amphioxus notochord cells and to gain insights into the myogenic program in the notochord, we determined the spatial and temporal expre-ssion patterns of these muscle-related genes during amphioxus development. We found that BbNA1 (notochord actin), Amphi-Trop I (troponin I), Amphi-TPmyosin (tropo-myosin), Amphi-MHC2 (myosin heavy chain), Amphi-nMRLC (notochord-specific myosin regulatory light chain), Amphi-nTitin/MLCK (notochord-specific titin/myosin light chain kinase), Amphi-MLP/CRP3 (muscle LIM protein), and Amphi-nCalponin (notochord-specific calponin) are expres-sed with characteristic patterns in notochord cells, including the central cells, dorsally located cells, and ventrally located cells, suggesting that each notochord cell has a unique molecular architecture that may reflect its function. In addition, we characterized two MyoD genes (Amphi-MyoD1 and Amphi-MyoD2) to gain insight into the genetic circuitry governing the formation of the notochord muscle. One of the MyoD genes (Amphi-MyoD2) is expressed in the central notochord cells, and the coexistence of Amphi-MyoD2 transcripts along with the Amphi-MLP/CRP3 transcripts implies the participation of Amphi-MyoD2 in the myogenic program in the notochord muscle.

Amino Acid Sequence↗

PubMed1994

Quantitative analyses of cell behaviors underlying notochord formation and extension in mouse embryos.

BACKGROUND: Formation and extension of the notochord (i.e., notogenesis) is one of the earliest and most obvious events of axis development in vertebrate embryos. In birds and mammals, prospective notochord cells arise from Hensen's node and come to lie beneath the midline of the neural plate. Throughout the period of neurulation, the notochord retains its close spatial relationship with the developing neural tube and undergoes rapid extension in concert with the overlying neuroepithelium. METHODS: In the present study, we examined notochord development quantitatively in mouse embryos. C57BL/6 mouse embryos were collected at 8, 8.5, 9, 9.5, and 10 days of gestation. They were then embedded in paraffin and sectioned transversely. Serial sections from 21 embryos were stained with Schiff's reagent according to the Feulgen-Rossenbeck procedure and used for quantitative analyses of notochord extension. RESULTS: Quantitative analyses revealed that extension of the notochord involves cell division within the notochord proper and cell rearrangement within the notochordal plate (the immediate precursor of the notochord). In addition, extension of the notochord involves cell accretion, that is, the addition of cells to the notochord's caudal end, a process that involves considerable cell rearrangement at the notochordal plate-node interface. CONCLUSIONS: Extension of the mouse notochord occurs similarly to that described previously for birds (Sausedo and Schoenwolf, 1993 Anat. Rec. 237:58-70). That is, in both birds (i.e., quail and chick) and mouse embryos, notochord extension involves cell division, cell rearrangement, and cell accretion. Thus higher vertebrates utilize similar morphogenetic movements to effect notogenesis.

Animals↗

PubMed2001

Cell interactions underlying notochord induction and formation in the chick embryo.

The development of the notochord in the chick is traditionally associated with Hensen's node (the avian equivalent of the organizer). However, recent evidence has shown that two areas outside the node (called the inducer and responder) are capable of interacting after ablation of Hensen's node to form a notochord. It was not clear from these studies what effect (if any) signals from these areas had on normal notochord formation. A third area, the postnodal region, may also contribute to notochord formation, although this has also been questioned. Using transection and grafting experiments, we have evaluated the timing and cellular interactions involved in notochord induction and formation in the chick embryo. Our results indicate that the rostral primitive streak, including the node, is not required for formation of the notochord in rostral blastoderm isolates transected at stages 3a/b. In addition, neither the postnodal region nor the inducer is required for the induction and formation of the most rostral notochordal cells. However, inclusion of the inducer results in considerable elongation of the notochord in this experimental paradigm. Our results also demonstrate that the responder per se is not required for notochord formation, provided that at least the inducer and postnodal region are present, although in the absence of the responder, formation of the notochord occurs far less frequently. We also show that the node is not specified to form notochord until stage 4 and concomitant with this, the inducer loses its ability to induce notochord from the responder. The coincident timing of these changes in the node and inducer suggests that notochord specification and the activity of the inducer are regulated through a negative feedback loop. We propose a model relating our results to the induction of head and trunk organizer activity in the node.

Animals↗

PubMed1994

Induction of notochord during ascidian embryogenesis.

The tadpole larva of solitary ascidians has 40 notochord cells in its tail. Of these cells, 32 in the anterior and middle part of the tail are derived from the A-line blastomeres, while 8 in the posterior part of the tail originate from the B-line blastomeres. Previous experiments involving continuous dissociation of daughter blastomeres from the first cleavage to the 110-cell stage suggested that cellular interactions may be involved in the formation of notochord cells. In the present study, the presumptive-notochord blastomeres isolated from the 32-cell embryos did not develop features of notochord. These results suggest that cellular interactions may be required for the fate specification of notochord, that is to say, notochord formation occurs as a result of inductive interaction between blastomeres. In order to confirm the involvement of induction in the determination of notochord and to identify the inducer blastomeres, the presumptive-notochord blastomeres at the 32-cell stage were coisolated or recombined with one of the surrounding blastomeres in a series of experiments. The results suggested that, for the A-line precursors, notochord differentiation occurs as the result of an inductive influence from vegetal blastomeres that include the presumptive-endoderm blastomeres and the presumptive-notochord blastomeres themselves. It was also suggested that induction of notochord is complete by the 64-cell stage and that inductive interactions have to be initiated before the decompaction of blastomeres during the 32-cell stage. Ascidians are Urochordata and are closely related to vertebrates. In vertebrates, it is well known that inductive interactions play a crucial role in the determination of notochord. It appears, therefore, that induction of notochord is common throughout the phylum Chordata.

Alkaline Phosphatase↗

PubMed1996

Age-dependent inhibition of neural crest migration by the notochord correlates with alterations in the S103L chondroitin sulfate proteoglycan.

In avian embryos, the notochord inhibits neural crest migration, resulting in the absence of neural crest cells from the perinotochordal space. Here, we test whether temporal changes in the ability of the notochord to inhibit neural crest migration correlate with alterations in the S1O3L chondroitin sulfate proteoglycan (CSPG). Because CSPGs are abundant in the perinotochordal space and the inhibitory effects of the notochord are chondroitinase sensitive both in vivo and in vitro, we examined the distribution and biochemical nature of a large CSPG whose core protein is recognized by the S103L antibody. The S103L CSPG is specific to the perinotochordal space during the course of neural crest migration and codistributes with the HNK-1 carbohydrate. Biochemical characterization reveals that the S103L CSPG bears the HNK-1 epitope and is the only HNK-l immunoreactive proteoglycan present around the notochord at these stages. Following neural crest migration, the S103L CSPG staining is maintained in the perinotochordal region and also is expressed later in cartilage. In 4-day-old embryos, however, the S103L CSPG undergoes a reduction of HNK-1 immunoreactivity. To examine the temporal nature of the notochord's inhibitory ability, we assayed the effects, on neural crest migration of grafting notochords from 2- to 5-day-old donor quail embryos into 2-day-old host chick embryos. Donor notochords from 2- to 3-day-old embryos inhibit neural crest cell migration, whereas the degree of inhibition is reduced or absent when notochords are derived from > or = 4-day-old donors. This suggests that older notochords lose their inhibitory ability. Interestingly, preincubation of younger notochords with the HNK-1 antibody blocks the inhibitory effect, suggesting that glycosylation of the perinotochordal matrix may be important. The time when the notochord loses its inhibitory ability as assessed by our in vivo grafting assay correlates with the biochemical and immunocytochemical changes in the notochordal S103L antigen. These data suggest that a species of S103L CSPG, which is expressed by the early notochord and bears the HNK-1 epitope, may be important for the inhibition of neural crest migration.

Animals↗

PubMed1997

The Danforth's short tail mutation acts cell autonomously in notochord cells and ventral hindgut endoderm.

Danforth's short tail (Sd) is a semidominant mutation in mouse affecting the axial skeleton and urogenital system. The notochord is the first visibly abnormal structure in mutant embryos, and disintegrates beginning around embryonic day 9.5 along its entire length, suggesting an essential role for Sd in notochord development and maintenance. Here, we report on the fate of Sd/+ and Sd/Sd cells in chimeric embryos. Up to day 9-9.5, Sd cells contributed efficiently to the notochord of chimeric embryos. In advanced day 9.5 embryos, Sd cells were less abundant in the posterior-most region of the notochord and in the notochordal plate. During subsequent development, Sd cells were specifically lost from the notochord and replaced by wild-type cells. In Sd/+<-->+/+ chimeras, the notochord appeared histologically and functionally normal, leading to a rescue of the mutant phenotype. However, strong Sd/Sd<-->+/+ chimeras showed malformations of the axial skeleton and urogenital system. All Sd/Sd<-->+/+ chimeras with malformations of the axial skeleton also had kidney defects, whereas chimeras without vertebral column defects had highly chimeric kidneys that appeared normal, suggesting that the urogenital malformations arise secondarily to impaired posterior development caused by the degenerating notochord. Sd mutant cells also were specifically absent from the ventral portion of the hindgut, whereas they contributed efficiently to the dorsal region, implying the existence of distinct cell populations in the dorsal and ventral hindgut. Our findings demonstrate that the Sd mutation acts cell autonomously in cells of the notochord and ventral hind gut. Sd leads to the degeneration of notochord cells and the number or allocation of notochord precursors from the tail bud to the notochordal plate seems impaired, whereas notochord formation from the node appears to be unaffected.

Animals↗