Stomodeal Ectoderm Research Articles

English

Ameloblastomas are a class of odontogenic tumors, which arise from developmental remnants in the oral tissue. Although the cellular and molecular mechanisms resulting in development of ameloblastoma are poorly understood, it is generally accepted that they exhibit an odontogenic source and originate from epithelial cells associated with tooth development. The epithelial sources in the oral tissue that can cause ameloblastomas include enamel organ, reduced enamel epithelium, rests of Malassez, and rests of Serres. These remnants originate from the stomodeal ectoderm, which give rise to the oral epithelium that initiate and guide tooth development as the embryo develops. It is of great clinical value to understand the developmental origin of these epithelial components and their histology, since the ameloblastomas display histopathological similarities to their structures.

Rathke’s pouch remnant and its regression process in the prenatal period

During ontogeny, part of Rathke's pouch, a physiologically superior pouching of the stomodeal ectoderm, may remain, forming the usual anomaly known as Rathke's cleft cyst. More rarely, however, the entire pouch (i.e., the craniopharyngeal canal) remains, resulting in transsphenoidal meningoencephalocele. This study is aimed to provide a better understanding of the pathogenesis. We histologically evaluated the inferior protrusion of the putative hypophysial fossa in 35 embryonic and fetal heads, respectively (15 at 5-8weeks and 20 at 12-16weeks of gestation). In 3 of the 35 specimens, we observed a complete cleft originating from the adenohypophysis, passing through the sphenoid and connecting with the pharyngeal epithelium or pharyngobasilar fascia. In another 18 specimens, we observed a duct-like structure protruding from the fossa and ending in the sphenoid. The sellar protrusion contained vein-like structures and debris of red blood cells. The protrusion was located on the anterior or anterosuperior side of the notochord. No ossification center was observed around the sellar region of the embryos. Although ossification occurred in 12 of the 20 fetuses, nine of the latter showed no evidence of cleft or protrusion, indicating that the incidence of Rathke's pouch remnant was lower in the fetuses (11/20) than in the embryos (11/15). Rathke's pouch may be closed by ossification of the sphenoid, but increased cell proliferation and/or large amounts of degenerated veins may provide a structure resistant to the mechanical pressure caused by ossification.

Spontaneous involution of a Rathke′s cleft cyst in a patient with normal cortisol secretion

Background:Rathke's cleft cyst (RCC) is a lesion derived from maldeveloped remnants of a dorsal invagination of the stomodeal ectoderm (Rathke's pouch). Although commonly found on autopsy, these lesions rarely become symptomatic during an individual's lifetime. When symptoms occur, they most often include headaches, visual disturbances, and/or varying degrees of hypopituitarism. The natural history remains unclear. The current standard of care includes surgical drainage and biopsy of the cyst wall or surgical resection of symptomatic lesions; however, debate exists regarding the management of asymptomatic lesions. Rare reports of spontaneously resolving RCC can be found in the literature.Case Description:We describe the management of a case of RCC in an 8½-year-old girl who presented with a history of growth deceleration since 4 years of age and near-growth arrest since 7 years of age. Her parents also described a tendency towards polydipsia since she was 2 years of age. Endocrine evaluation revealed growth hormone deficiency, central hypothyroidism, and diabetes insipidus, but normal cortisol secretion. The patient experienced no symptoms characteristic of intracranial or sellar mass. Neurologic examination was normal; formal ophthalmologic examination revealed no deficits. The magnetic resonance imaging (MRI) was consistent with RCC. The patient was treated medically for her hormone deficiencies. Over the next year, her sellar mass spontaneously involuted. Twenty-seven months after her initial presentation to our clinic, imaging revealed no sellar mass; the patient remained on hormone replacement therapy.Conclusion:Although the natural history of RCC requires further study, observation with serial MRI may be an acceptable management strategy in the absence of debilitating symptoms.

Direct development of neurons within foregut endoderm of sea urchin embryos

Although it is well established that neural cells are ectodermal derivatives in bilaterian animals, here we report the surprising discovery that some of the pharyngeal neurons of sea urchin embryos develop de novo from the endoderm. The appearance of these neurons is independent of mouth formation, in which the stomodeal ectoderm joins the foregut. The neurons do not derive from migration of ectoderm cells to the foregut, as shown by lineage tracing with the photoactivatable protein KikGR. Their specification and development depend on expression of Nkx3-2, which in turn depends on Six3, both of which are expressed in the foregut lineage. SoxB1, which is closely related to the vertebrate Sox factors that support a neural precursor state, is also expressed in the foregut throughout gastrulation, suggesting that this region of the fully formed archenteron retains an unexpected pluripotency. Together, these results lead to the unexpected conclusion that, within a cell lineage already specified to be endoderm by a well-established gene regulatory network [Peter IS, Davidson EH (2010) Dev Biol 340:188-199], there also operates a Six3/Nkx3-2-dependent pathway required for the de novo specification of some of the neurons in the pharynx. As a result, neuroendoderm precursors form in the foregut aided by retention of a SoxB1-dependent pluripotent state.

Generation of Prolactin-Like Neurons in the Dorsal Strand of Ascidians

The adult ascidian neural complex forms from a thin tube called the neurohypophyseal duct and from the primordium of the cerebral ganglion from the sensory vesicle in metamorphosing larvae. Neurohypophyseal duct cells, located in the anterior left side of the sensory vesicle of swimming larvae, are derived from the anterior embryonic neural plate, which expresses common transcription factors in vertebrates and urochordates. The cerebral ganglion primordium is probably derived from the posterior sensory vesicle during metamorphosis. After metamorphosis begins, the duct elongates anteriorly and fuses with the stomodeal ectoderm, where the dorsal tubercle, a large ciliated structure that opens into the upper part of the pharynx, later develops. The rudiment of the cerebral ganglion and the duct elongate posteriorly. The duct also differentiates into the neural gland. The dorsal wall of the neural gland in adult ascidians has a thick epithelium (placode), the central part of which forms the dorsal strand by repeated invaginations along the visceral nerve. Both gonadotropin-releasing hormone (GnRH) neurons and prolactin-like (non-GnRH) neurons are generated in the dorsal strand and migrate to the cerebral ganglion along the visceral nerve throughout adulthood. Thus, the epithelium derived from the neurohypophyseal duct possesses neurogenic potential to generate neural stem cells of the central (cerebral ganglion) and peripheral (dorsal strand) nervous systems. The generation of prolactin-like neurons and their migration into the brain with GnRH neurons suggest that the ascidian dorsal strand is homologous to the craniate olfactory placode, and provide unequivocal support for the existence of the clade Olfactores.

Fluorescent in situ hybridization reveals multiple expression domains for SpBrn1/2/4 and identifies a unique ectodermal cell type that co-expresses the ParaHox gene SpLox

Here we report on the expression of two transcription factors previously reported to be involved in endodermal patterning, SpLox and SpBrn1/2/4. We describe three distinct domains of expression of the pou-domain gene SpBrn1/2/4. Endodermal expression of this gene is restricted to the foregut. SpBrn1/2/4 is also expressed in two distinct ectodermal domains: throughout the stomodeal ectoderm, and within cells scattered throughout the ciliated band. The ParaHox gene SpLox is demonstrated to also be expressed in ectodermal bilateral cell pairs in prism and early pluteus stage larvae. Double fluorescent in situ hybridization reveals that these cell pairs co-express both SpLox and SpBrn1/2/4, thus marking a novel cell type within the ciliary band of the sea urchin larvae.

Epithelial‐Mesenchymal Interactions during Facial Development in Mice

Previously, we determined that when avian neural crest cells reach the Frontonasal Process (FNP) at Hamburger and Hamilton Stage 20 (HH), Sonic hedgehog (Shh) expression is induced in the stomodeal ectoderm and forms a boundary with a Fibroblast growth factor 8 (Fgf8) expression domain. The ectoderm flanking this boundary controls FNP growth and patterning, but the mechanisms used by this tissue to pattern the face are unknown. In this work, we examined the facial ectoderm of mice to determine whether a similar signaling center exists and how it functions. Fgf8 is expressed in the distal facial ectoderm at e9.5 and continues to be expressed at e10. At e10 Shh is expressed in both median nasal processes and forms a boundary with Fgf8 in each process. Next, we grafted the mouse ectoderm from e10 embryos onto the dorsal FNP of HH 25 chick embryos. Twenty‐four hours after transplantation the graft (n=4) maintained expression of Fgf8, Shh, Bmp‐2, Bmp‐4, and Bmp‐7, and in the neural crest mesenchyme we observed up‐regulation of Bmp‐4, Bmp‐7, and Msx‐1 and ‐2. By 13 days of development the chimeras exhibited a duplication of the upper beak that was comprised of correctly patterned bone and cartilage (n=4). We observed no hair follicles, but we did observe ectopic egg teeth. These results indicate that in mice a signaling center located in the ectoderm of each median nasal process regulates development of the middle and upper face by inducing signaling molecules that govern skeletogenesis within neural crest mesenchyme. The organization of this center is different from that in the chick where a single Shh domain spans the stomodeal ectoderm and forms a continuous boundary with Fgf8 in the FNP.NIH/NIDCR R01‐1DE018234 to R.M.

Repression of mesodermal fate byfoxa, a key endoderm regulator of the sea urchin embryo

The foxa gene is an integral component of the endoderm specification subcircuit of the endomesoderm gene regulatory network in the Strongylocentrotus purpuratus embryo. Its transcripts become confined to veg2, then veg1 endodermal territories, and, following gastrulation, throughout the gut. It is also expressed in the stomodeal ectoderm. gatae and otx genes provide input into the pregastrular regulatory system of foxa, and Foxa represses its own transcription, resulting in an oscillatory temporal expression profile. Here, we report three separate essential functions of the foxa gene: it represses mesodermal fate in the veg2 endomesoderm; it is required in postgastrular development for the expression of gut-specific genes; and it is necessary for stomodaeum formation. If its expression is reduced by a morpholino, more endomesoderm cells become pigment and other mesenchymal cell types, less gut is specified, and the larva has no mouth. Experiments in which blastomere transplantation is combined with foxa MASO treatment demonstrate that, in the normal endoderm, a crucial role of Foxa is to repress gcm expression in response to a Notch signal, and hence to repress mesodermal fate. Chimeric recombination experiments in which veg2, veg1 or ectoderm cells contained foxa MASO show which region of foxa expression controls each of the three functions. These experiments show that the foxa gene is a component of three distinct embryonic gene regulatory networks.

Early Hedgehog signaling from neural to oral epithelium organizes anterior craniofacial development

Hedgehog (Hh) signaling plays multiple roles in the development of the anterior craniofacial skeleton. We show that the earliest function of Hh is indirect, regulating development of the stomodeum, or oral ectoderm. A subset of post-migratory neural crest cells, that gives rise to the cartilages of the anterior neurocranium and the pterygoid process of the palatoquadrate in the upper jaw, condenses upon the upper or roof layer of the stomodeal ectoderm in the first pharyngeal arch. We observe that in mutants for the Hh co-receptor smoothened (smo) the condensation of this specific subset of crest cells fails, and expression of several genes is lost in the stomodeal ectoderm. Genetic mosaic analyses with smo mutants show that for the crest cells to condense the crucial target tissue receiving the Hh signal is the stomodeum, not the crest. Blocking signaling with cyclopamine reveals that the crucial stage, for both crest condensation and stomodeal marker expression, is at the end of gastrulation--some eight to ten hours before crest cells migrate to associate with the stomodeum. Two Hh genes, shh and twhh, are expressed in midline tissue at this stage, and we show using mosaics that for condensation and skeletogenesis only the ventral brain primordium, and not the prechordal plate, is an important Hh source. Thus, we propose that Hh signaling from the brain primordium is required for proper specification of the stomodeum and the stomodeum, in turn, promotes condensation of a subset of neural crest cells that will form the anterior neurocranial and upper jaw cartilage.

Craniofacial development in the talpid3 chicken mutant

The talpid 3 chicken mutant has a pleiotropic phenotype including polydactyly and craniofacial abnormalities. Limb polydactyly in talpid 3 suggests a gain of Hedgehog (Hh) signaling, whereas, paradoxically, absence of midline facial structures suggests a loss of Hh function. Here we analyze the status of Shh signaling in the talpid 3 mutant head. We show that Shh expression domains are lost from the talpid 3 head—in hindbrain, midbrain, zona limitans intrathalamica, and stomodeal ectoderm—and that direct targets of Hedgehog signaling, Ptc1, Ptc2, and Gli1, are also absent even in areas associated with primary Shh expression. These data suggest that the talpid 3 mutation leads to defective activation of the Shh pathway and, furthermore, that tissue-to-tissue transduction of Shh expression in the developing head depends on Hh pathway activation. Failure to activate the Shh pathway can also explain absence of floor plate and Hnf-3β and Netrin-1 expression in midbrain and hindbrain and absence of Fgf-8 expression in commissural plate. Other aspects of gene expression in the talpid 3 head, however, suggest misspecification, such as maintenance of floor plate-like gene expression in telencephalon. In branchial arches and lower jaw, where Shh is expressed, changes in expression of genes involved in patterning and mesodermal specification suggest both gain and loss of Hedgehog function. Thus, analysis of gene expression in talpid 3 head shows that, as in talpid 3 limb, expression of some genes is lost, while others are ectopically expressed. Unlike the limb, many head regions depend on Hh induction of a secondary domain of Shh expression, and failure of this induction in talpid 3, together with the inability to activate the Shh pathway, explain the loss-of-function head phenotype. This gene expression analysis in the talpid 3 head also confirms and extends knowledge of the importance of Shh signaling and the balance between activation and repression of Shh targets in many aspects of craniofacial morphogenesis.

Pitx homeobox genes in Ciona and amphioxus show left-right asymmetry is a conserved chordate character and define the ascidian adenohypophysis.

All vertebrates have directional asymmetries in the organization of their internal organs. In jawed vertebrates, development of asymmetry is controlled by a conserved molecular pathway that includes Pitx2, which is expressed by lateral plate mesoderm cells on the left side of the embryo. Pitx2 is a member of the Pitx homeobox gene family, the expression of which also marks stomodeal ectoderm and the adenohypophysis. Here we report the characterization of Pitx genes from Branchiostoma floridae (an amphioxus) and Ciona intestinalis (a urochordate), representatives of two basal chordate lineages and successively deeper outgroups to the vertebrates. Expression of B. floridae Pitx is similar to that reported from B. belcheri, a different amphioxus species. Expression of the Ciona Pitx ortholog in the embryonic primordial pharynx and adult neural complex leads us to propose the Ciona primordial pharynx and ciliated funnel are homologous to the adenohypophyseal placode and adenohypophysis, respectively. Additionally, in both species we identify asymmetrical left-sided expression of Pitx genes during embryonic development. This shows that asymmetrical Pitx gene expression, and by inference directional asymmetry, evolved before the radiation of living chordates and should be considered a chordate character.

Cloning and expression of a Pitx homeobox gene from the lamprey, a jawless vertebrate.

The Pitx homeobox gene family has important roles in vertebrate pituitary, eye, branchial arch, hindlimb and brain development, as well as a key function in regulating left-right asymmetry. Here we report the isolation of a Pitx gene, PitxA, from two lamprey species, Lampetra planeri and Petromyzon marinus. Molecular phylogenetics show PitxA is most closely related to the Pitx1 and Pitx2 genes of jawed vertebrates, however resolution in the trees is insufficient to determine if PitxA is orthologous to a specific jawed vertebrate gene. In situ hybridisation studies show lamprey PitxA is expressed in the developing nasohypohyseal system and stomodeal ectoderm from early development through to early ammocoette larvae. PitxA expression was also detected in several areas of the developing brain, in the developing optic system, in pharyngeal endoderm and endostyle and in the lateral somite. These results show some key aspects of Pitx gene expression in gnathostomes are primitive for all living vertebrates.

The paired-type homeobox gene Dmbx1 marks the midbrain and pretectum

We have isolated a paired-type homeobox gene Dmbx1, previously known as Atx (Development 128 (2001) 4789), from chick and mouse. Sequence similarity reveals that this gene is highly related to the Otx genes. Expression of Dmbx1 commences during gastrulation, when transcripts are detected in a crescent around the anterior neural plate. As development progresses, Dmbx1 marks the prospective midbrain and pretectum. Dmbx1 shares its caudal border of expression with Otx2, while expression is sharply delimited rostrally by the synencephalic–parencephalic boundary, later becoming restricted to the posterior synencephalon. At later stages, Dmbx1 is expressed in dynamic domains of the hindbrain and spinal cord. Additional sites of expression comprise stomodeal ectoderm and foregut endoderm, presomitic mesoderm, and the nasal pit.

Hypophyseal Development in Vertebrates from Amphibians to Mammals

Classically, it has been widely accepted that epithelial hypophysis develops from the stomodeal ectoderm. This notion was based on purely morphological observation of normal specimens. Recently, evidence is being accumulated that indicates another lineage for the developmental origin of adenohypophysis. This minireview focuses on several series of experimental works that have demonstrated a neuroectodermal origin of the hypophysis in vertebrates from amphibians to mammals. Phylogenetic consideration of the pituitary-like structures of prechordal animals is also presented.

Group B sox genes that contribute to specification of the vertebrate brain are expressed in the apical organ and ciliary bands of hemichordate larvae.

We have identified and characterized the sequence and expression of two Group B Sox genes in the acorn worm, Ptychodera flava. One sequence represents a Group B1 Sox gene and is designated Pf-SoxB1; the other is a Group B2 Sox gene and is designated Pf-SoxB2. Both genes encode polypeptides with an HMG domain in the N-terminal half. Whole-mount in situ hybridization to embryonic and larval stages of P. flava shows that the two genes are expressed in rather similar patterns at these stages. Expression is first detected in the cells of the blastula and subsequently localizes to the ectoderm during gastrulation. As the mouth forms, expression becomes concentrated in the stomodeum region. During morphogenesis of the tornaria larva, expression in the stomodeal ectoderm remains prominent around the mouth and under the oral hood. Later the genes are prominently upregulated in the ciliary bands and the apical organ. These results provide additional evidence that genes playing essential roles in the formation of the chordate dorsal central nervous system function in the development of the ciliary bands and apical organ, neural structures of this non-chordate deuterostome larva.

Neural crest and tooth morphogenesis.

Mammalian teeth develop from two types of cells: stomodeal ectoderm, which forms ameloblasts, and cranial neural-crest-derived (ecto) mesenchyme cells, which form odontoblasts and cementoblasts. These two cell types, juxtaposed in the developing oral cavity, interact to control the entire process of tooth initiation, morphogenesis, and cytodifferentiation. Cell-cell signaling pathways and their target nuclear factors have been identified as key mediators of the progressively complex exchange of information between ectoderm and ectomesenchyme. The constantly changing direction of the reciprocal signaling and cell responses between ectoderm and ectomesenchyme enables cells to monitor their relative spatial positions and differentiated states continuously. The least understood of the early processes in tooth development are morphogenesis and patterning. From a seemingly uniform layer of oral ectoderm and underlying mass of ectomesenchyme, different types (shapes) of teeth develop in different positions. Tooth type is determined very early in development, before the overt onset of morphogenesis. Thus, the early ectoderm-ectomesenchyme cell interactions must in some way either create or respond to positional differences in the jaw primordia.

Foregut endoderm is required at head process stages for anteriormost neural patterning in chick.

Anterior definitive endoderm, the future pharynx and foregut lining, emerges from the anterior primitive streak and Hensen's node as a cell monolayer that replaces hypoblast during chick gastrulation. At early head process stages (4+ to 6; Hamburger and Hamilton) it lies beneath, lateral to and ahead of the ingressed axial mesoderm. Removal of the monolayer beneath and ahead of the node at stage 4 is followed by normal development, the removed cells being replaced by further ingressing cells from the node. However, similar removal during stages 4+ and 5 results in a permanent window denuded of definitive endoderm, beneath prechordal mesoderm and a variable sector of anterior notochord. The foregut tunnel then fails to form, heart development is confined to separated lateral regions, and the neural tube undergoes no ventral flexures at the normal positions in brain structure. Reduction in forebrain pattern is evident by the 12-somite stage, with most neuraxes lacking telencephalon and eyes, while forebrain expressions of the transcription factor genes GANF and BF1, and of FGF8, are absent or severely reduced. When the foregut endoderm removal is delayed until stage 6, later forebrain pattern appears once again complete, despite lack of foregut formation, of ventral flexure and of heart migration. Important gene expressions within axial mesoderm (chordin, Shh and BMP7) appear unaffected in all embryos, including those due to be pattern-deleted, during the hours following the operation when anterior brain pattern is believed to be determined. A specific system of neural anterior patterning signals, rather than an anterior sector of the initially neurally induced area, is lost following operation. Heterotopic lower layer replacement operations strongly suggest that these patterning signals are positionally specific to anteriormost presumptive foregut. The homeobox gene Hex and the chick Frizbee homologue Crescent are both expressed prominently within anterior definitive endoderm at the time when removal of this tissue results in forebrain defects, and the possible implications of this are discussed. The experiments also demonstrate how stomodeal ectoderm, the tissue that will, much later, form Rathke's pouch and the anterior pituitary, is independently specified by anteriormost lower layer signals at an early stage.

Tissue Interactions in the Induction of Anterior Pituitary: Role of the Ventral Diencephalon, Mesenchyme, and Notochord

Rathke's pouch, the epithelial primordium of the anterior pituitary, differentiates in close topographical and functional association with the ventral diencephalon. It is still not known whether the ventral diencephalon acts as the initial inducer of pituitary development. The roles of the adjacent mesenchyme and notochord, two other tissues located in close proximity to Rathke's pouch, in this process are even less clear. In this report we describe an in vitro experimental system that reproduces the earliest steps of anterior pituitary development. We provide evidence that the ventral diencephalon from 2- to 4-day-old chick embryos is able to function as an inducer of pituitary development and can convert early chick embryonic head ectoderm, which is not involved normally in pituitary development, into typical anterior pituitary tissue. This induction is contact-dependent. In our experimental system, there is a requirement for the supporting action of mesenchyme, which is independent of the mesenchyme source. Transplantation of the notochord into the lateral head region of a six-somite chick embryo induces an epithelial invagination, suggesting that the notochord induces the outpouching of the roof of the stomodeal ectoderm that results in formation of Rathke's pouch and causes the close contact between this ectoderm and the ventral diencephalon. Finally, we demonstrate that the ventral diencephalon from e9.5–e11.5 mouse embryos is also an efficient inducer of anterior pituitary differentiation in chick embryonic lateral head ectoderm, suggesting that the mechanism of anterior pituitary induction is conserved between mammals and birds, using the same, or similar, signaling pathways.

Pituitary Homeobox 1 (Ptx1) Is Differentially Expressed during Pituitary Development*

Pituitary homeobox 1 (Ptx1) is a homeodomain-containing transcription factor acting on transcription of all pituitary hormone genes. Its expression is first detected in the stomodeal ectoderm and is maintained in all derivatives of this structure, including Rathke's pouch. We now show that Ptx1 is expressed in all pituitary cells but that it is differentially expressed in different lineages at both the messenger RNA and protein levels. On day 12.5 of mouse embryonic development, cells expressing the highest levels of Ptx1 are restricted to the forming pars tuberalis, also called the rostral tip, a region where the first alpha-glycoprotein subunit-expressing cells appear. Coimmunolocalization studies reveal that alpha-glycoprotein subunit-positive cells express the highest levels of Ptx1 throughout development and in the adult gland. The quantitative differences in Ptx1 expression in pituitary cell lineages may relate to a role in cell proliferation, lineage commitment, and/or the control of organ development.

Pituitary Homeobox 1 (Ptx1) Is Differentially Expressed during Pituitary Development

Pituitary homeobox 1 (Ptx1) is a homeodomain-containing transcription factor acting on transcription of all pituitary hormone genes. Its expression is first detected in the stomodeal ectoderm and is maintained in all derivatives of this structure, including Rathke’s pouch. We now show that Ptx1 is expressed in all pituitary cells but that it is differentially expressed in different lineages at both the messenger RNA and protein levels. On day 12.5 of mouse embryonic development, cells expressing the highest levels of Ptx1 are restricted to the forming pars tuberalis, also called the rostral tip, a region where the first α-glycoprotein subunit-expressing cells appear. Coimmunolocalization studies reveal that α-glycoprotein subunit-positive cells express the highest levels of Ptx1 throughout development and in the adult gland. The quantitative differences in Ptx1 expression in pituitary cell lineages may relate to a role in cell proliferation, lineage commitment, and/or the control of organ development.