embryology Embryology (from Greek ἔμβρυον, ''embryon'', "the unborn, embryo"; and -λογία, '' -logia'') is the branch of animal biology that studies the prenatal development of gametes (sex cells), fertilization, and development of embryos and ...

and

prenatal development Prenatal development () includes the development of the embryo and of the fetus during a viviparous animal's gestation. Prenatal development starts with fertilization, in the germinal stage of embryonic development, and continues in fetal devel ...

, the dental papilla is a condensation of

ectomesenchymal Ectomesenchyme has properties similar to mesenchyme. The origin of the ectomesenchyme is disputed. It is either like the mesenchyme, arising from mesodermic cells, or conversely arising from neural crest cells. The neural crest is a critical group ...

cells called

odontoblast In vertebrates, an odontoblast is a cell of neural crest origin that is part of the outer surface of the dental pulp, and whose biological function is dentinogenesis, which is the formation of dentin, the substance beneath the tooth enamel on t ...

s, seen in

histologic Histology, also known as microscopic anatomy or microanatomy, is the branch of biology which studies the microscopic anatomy of biological tissues. Histology is the microscopic counterpart to gross anatomy, which looks at larger structures vis ...

sections of a developing tooth. It lies below a cellular aggregation known as the

enamel organ The enamel organ, also known as the dental organ, is a cellular aggregation seen in a developing tooth and it lies above the dental papilla. The enamel organ which is differentiated from the primitive oral epithelium lining the stomodeum.The enam ...

. The dental papilla appears after 8–10

week A week is a unit of time equal to seven days. It is the standard time period used for short cycles of days in most parts of the world. The days are often used to indicate common work days and rest days, as well as days of worship. Weeks are ofte ...

s intra uteral life. The dental papilla gives rise to the

dentin Dentin () (American English) or dentine ( or ) (British English) ( la, substantia eburnea) is a calcified tissue of the body and, along with enamel, cementum, and pulp, is one of the four major components of teeth. It is usually covered by ena ...

and

pulp Pulp may refer to: * Pulp (fruit), the inner flesh of fruit Engineering * Dissolving pulp, highly purified cellulose used in fibre and film manufacture * Pulp (paper), the fibrous material used to make paper * Molded pulp, a packaging material ...

of a

tooth A tooth ( : teeth) is a hard, calcified structure found in the jaws (or mouths) of many vertebrates and used to break down food. Some animals, particularly carnivores and omnivores, also use teeth to help with capturing or wounding prey, tear ...

. The enamel organ, dental papilla, and

dental follicle The dental follicle, also known as dental sac, is made up of mesenchymal cells and fibres surrounding the enamel organ and dental papilla of a developing tooth. It is a vascular fibrous sac containing the developing tooth and its odontogenic organ ...

together forms one unit, called the tooth germ. This is of importance because all the tissues of a tooth and its supporting structures form from these distinct cellular aggregations. Similar to

, the dental papilla has a very rich blood supply and provides nutrition to the

Embryology

Formation of dental papilla occurs in the Cap stage of

Odontogenesis Tooth development or odontogenesis is the complex process by which teeth form from embryonic cells, grow, and erupt into the mouth. For human teeth to have a healthy oral environment, all parts of the tooth must develop during appropriate sta ...

The cap stage

The cap stage is the second stage of tooth development and occurs during the ninth or tenth week of prenatal development. Unequal proliferation of the tooth bud forms a three-dimensional cap shape. Overlying this cap structure is the

ectomesenchyme Ectomesenchyme has properties similar to mesenchyme. The origin of the ectomesenchyme is disputed. It is either like the mesenchyme, arising from mesodermic cells, or conversely arising from neural crest cells. The neural crest is a critical group ...

, which is attached to the

mesoderm The mesoderm is the middle layer of the three germ layers that develops during gastrulation in the very early development of the embryo of most animals. The outer layer is the ectoderm, and the inner layer is the endoderm.Langman's Medical E ...

al tissue known as the dental papilla superiorly, and lies within the epithelial concavity. Various types of differentiation occur at this stage; such as cytodifferentiation, histodifferentiation and morphodifferentation. Histodifferentiation is the differentiation of different tissue types during the development of an embryo/ undifferentiated group of cells. Furthermore, morphogenesis is a predominant physiological process during the cap stage. This is due to formation of

primordium A primordium (; plural: primordia; synonym: anlage) in embryology, is an organ or tissue in its earliest recognizable stage of development. Cells of the primordium are called primordial cells. A primordium is the simplest set of cells capable o ...

of the tooth. The

contains each of the primordial tissue types, essential for the development of successive teeth. These primordial tissues together form the enamel organ, dental papilla and dental sac. Also during the cap stage is the formation of a depression within the deepest part of each tooth bud of the

dental lamina The dental lamina is a band of epithelial tissue seen in histologic sections of a developing tooth. The dental lamina is first evidence of tooth development and begins (in humans) at the sixth week in utero or three weeks after the rupture of th ...

. The dental lamina is a band of epithelial tissue which connects the developing tooth bud to the oral epithelium. The dental lamina eventually disintegrates into small clusters of epithelium and is reabsorbed. The dental lamina is first evidence of tooth development and begins at the sixth week in utero. This is responsible for the cap like structure of the enamel organ. It is important to note that enamel is an ectodermal product as it is originally derived from

ectoderm The ectoderm is one of the three primary germ layers formed in early embryonic development. It is the outermost layer, and is superficial to the mesoderm (the middle layer) and endoderm (the innermost layer). It emerges and originates from t ...

which is the outermost of the three germ layers of the forming embryo. The other two are: the mesoderm and the

endoderm Endoderm is the innermost of the three primary germ layers in the very early embryo. The other two layers are the ectoderm (outside layer) and mesoderm (middle layer). Cells migrating inward along the archenteron form the inner layer of the gast ...

. It gives rise to the nervous system, sense organs, outer layer of the skin, teeth and the membrane lining the oral cavity (mouth). A section of the ectomesenchyme (a group of tissue made up of neurocrest cells which are present in the initial development of an embryo. This forms the hard and soft tissues of the neck and skull), condenses into a mass within the concavity of the cap of the enamel organ. This mass is now considered the dental papilla. Note that dental papilla is originally derived from ectomesenchyme. Ectomesenchyme (type of mesenchyme) is derived from

neural crest Neural crest cells are a temporary group of cells unique to vertebrates that arise from the embryonic ectoderm germ layer, and in turn give rise to a diverse cell lineage—including melanocytes, craniofacial cartilage and bone, smooth muscle, per ...

cells (NCCs). A

basement membrane The basement membrane is a thin, pliable sheet-like type of extracellular matrix that provides cell and tissue support and acts as a platform for complex signalling. The basement membrane sits between Epithelium, epithelial tissues including mesot ...

exists between the

and dental papilla which will be the site of the future

dentinoenamel junction The dentinoenamel junction or dentin-enamel junction (DEJ) is the boundary between the enamel and the underlying dentin that form the solid architecture of a tooth A tooth ( : teeth) is a hard, calcified structure found in the jaws (or mout ...

. The dentinoenamel junction is the surface at which the enamel and the dentin of the crown of a tooth are joined. The existing ectomesenchyme around the outside of the cap of the enamel organ then condenses into the dental sac. A

separate the enamel organ and the dental sac. The dental sac produces the

periodontium The periodontium is the specialized tissues that both surround and support the teeth, maintaining them in the maxillary and mandibular bones. The word comes from the Greek terms περί ''peri''-, meaning "around" and -''odont'', meaning "tooth". ...

in future development. The periodontium is the tissue that surrounds and supports the teeth. It includes the connective tissue and overlying keratinised membrane lining the oral cavity that surrounds the teeth, the periodontal ligament, cementum which provides a protective covering for the root surface and supporting alveolar bone

The Bell Stage

This is the fourth stage of

tooth development Tooth development or odontogenesis is the complex process by which teeth form from embryonic cells, grow, and erupt into the mouth. For human teeth to have a healthy oral environment, all parts of the tooth must develop during appropriate stag ...

which occurs between the eleventh and twelfth week of

. During this stage of

, the epithelial tooth germ forms a bell - shaped structure in the labio - lingual section and is characterised by the formation of the dental sac. The peripheral cells of the dental papilla undergo differentiation, growing larger in size and taking a columnar (uni-layered) form and are now referred to as

Odontoblast In vertebrates, an odontoblast is a cell of neural crest origin that is part of the outer surface of the dental pulp, and whose biological function is dentinogenesis, which is the formation of dentin, the substance beneath the tooth enamel on t ...

s (the outer part of the dental pulp). This differentiation begins at the apex of the dental papilla, gradually extending downwards. This differentiation occurs to supplement the development of the dental sac which is responsible for cementum, periodontal ligament and the

alveolar process The alveolar process () or alveolar bone is the thickened ridge of bone that contains the tooth sockets on the jaw bones (in humans, the maxilla and the mandible). The structures are covered by gums as part of the oral cavity. The synonymous ter ...

Epithelium Layers

- Inner * is separated from the peripheral cells of the dental papilla by a basement membrane and a cell free zone * rich in RNA but do not contain alkaline phosphatase -Outer * involved in the maintenance of the shape of the enamel and the environment * contain very big nuclei and have small quantities of the intra-cellular organelles involved in protein synthesis. The cells contact each other through desmosomes and gap junctions -Stratum Is concerned with: * the synthesis of proteins * the transport of materials to and from the enamel- forming cells in the internal enamel epithelium * the concentration of materials

The Apposition Stage and the Maturation Stage

During the apposition stage the enamel, dentin and

cementum Cementum is a specialized calcified substance covering the root of a tooth. The cementum is the part of the periodontium that attaches the teeth to the alveolar bone by anchoring the periodontal ligament.Illustrated Dental Embryology, Histology, a ...

are secreted in successive layers. The mesenchymal tissue of dental papilla and dental sac and the ectodermal tissue of enamel underg
induction
The outer cells of dental papilla are induced by preameloblasts (cells within the enamel from which a cell that takes part in forming dental enamel develops) to differentiate into odontoblasts (dentin-secreting cells). The odontoblasts undergo differentiation and

repolarization In neuroscience, repolarization refers to the change in membrane potential that returns it to a negative value just after the depolarization phase of an action potential which has changed the membrane potential to a positive value. The repolarizat ...

and result in formation of the dentin matrix/pre-dentin (the innermost section of the dentin, which is not mineralized and located adjacent to pulp tissues in the crown area and root area). The central cells of dental papilla form the

of the pulp during root development. These cells then become surrounded by newly formed dentin..

Differentiation

Ectomesenchymal cells will multiply continuously in a localized area such that when the bell stage of development is reached, both the epithelial component and the ectomesenchymal component will seem to have been surrounded by something that presents as a

fibrous Fiber or fibre (from la, fibra, links=no) is a #Natural fibers, natural or Fiber#Artificial fibers, artificial substance that is significantly longer than it is wide. Fibers are often used in the manufacture of other materials. The stronge ...

sac. Therefore, among a complicated mass of highly differentiated cells, it would appear to have three major components, which are: 1) ''The

Dental Follicle The dental follicle, also known as dental sac, is made up of mesenchymal cells and fibres surrounding the enamel organ and dental papilla of a developing tooth. It is a vascular fibrous sac containing the developing tooth and its odontogenic organ ...

'' → The ectomesenchymal cells which are part of the fibrous sac that have been formed 2) ''The Dental Papilla'' → The ectomesenchymal cells which are lying deep to the enamel organ 3) ''The Enamel Organ'' → purely the epithelial component The tissues which have been derived from each of the three components are: 1) ''The Dental Follicle'' → will develop to become the periodontal ligament, the cementum and the

alveolar bone The alveolar process () or alveolar bone is the thickened ridge of bone that contains the tooth sockets on the jaw bones (in humans, the maxilla and the mandible). The structures are covered by gums as part of the oral cavity. The synonymous ter ...

2) ''The Dental Papilla'' → will develop to become the dental pulp and the dentine 3) ''The Enamel Organ'' → will develop to create the enamel solely It is important to note that till this point, no dental tissues have been created yet. When all of the individual components of the tooth germ have become developed, the entire cell mass would have appeared to have migrated deeper into the underlying connective tissues. This phenomenon, which will continue throughout the whole life of the teeth, is most possibly due to the cell mass moving towards a rich blood supply that can be found in the deeper parts of the

mandible In anatomy, the mandible, lower jaw or jawbone is the largest, strongest and lowest bone in the human facial skeleton. It forms the lower jaw and holds the lower tooth, teeth in place. The mandible sits beneath the maxilla. It is the only movabl ...

(lower jaw) and the

maxilla The maxilla (plural: ''maxillae'' ) in vertebrates is the upper fixed (not fixed in Neopterygii) bone of the jaw formed from the fusion of two maxillary bones. In humans, the upper jaw includes the hard palate in the front of the mouth. The t ...

(upper jaw) The probable need for a rich blood supply would seem to show that the cell mass will soon be highly productive in the formation of dental tissues. Therefore, when the late bell stage of the tooth germ development has been reached, most of the cells would have been differentiated to an apparent endpoint where the cells will now begin their formative role when the first three stages of the tissue development are almost completed, and the tissues can now start to begin secreting.

Nerve and Vascular Supply during Early Development

Vascular Supply

Clusters of blood vessels are found branching out around the tooth germ in the dental follicle and going into the dental papilla during the cap stage. In the dental papilla the number of blood vessels increase and the matrix deposition will begin once the maximum is reached during the bell stage. Blood vessels going into the dental papilla are formed into groups that coincides with the positions of where the roots will develop in future. As time passes, the viability of the tissue is affected as the blood supply becomes steadily reduced in stages and the volume of pulpal tissue starts decreasing too.

Nerve Supply

During the bud to cap stage of tooth development, the pioneer nerve fibers head towards the developing tooth. The nerve fibers will branch out and create a rich

plexus In neuroanatomy, a plexus (from the Latin term for "braid") is a branching network of vessels or nerves. The vessels may be blood vessels (veins, capillaries) or lymphatic vessels. The nerves are typically axons outside the central nervous syste ...

around the tooth germ in that structure as the

is the clear target of these dental nerve fibers. The dental follicle is a fibrous sac that surrounds the odontogenic organ and developing tooth. The plexus is a system of connections of blood vessels, nerves, or

lymphatic vessel The lymphatic vessels (or lymph vessels or lymphatics) are thin-walled vessels (tubes), structured like blood vessels, that carry lymph. As part of the lymphatic system, lymph vessels are complementary to the cardiovascular system. Lymph vess ...

s. The plexus of Raschkow is a network of nerves immediately beneath the odonblast layer of the dentine, first described by J. Raschkow in 1835. However, the nerve fibers will only begin entering the dental papilla (pulp) when

Dentinogenesis {{Refimprove, date=September 2014 Dentinogenesis is the formation of dentin, a substance that forms the majority of teeth. Dentinogenesis is performed by odontoblasts, which are a special type of biological cell on the outer wall of dental pulps, an ...

starts. The timing is not similar to the establishment of the neural supply and the papillary vascular supply even though a feasible relationship has been assumed between the developing nerve and blood supplies. Furthermore, histo-chemistry studies have shown that in the makeup of pioneer nerve fibers heading towards the tooth germ, automatic nerve fibers are not present. Therefore, the starting innervation of the developing teeth is involved with the sensory innovation of the future

periodontal ligament The periodontal ligament, commonly abbreviated as the PDL, is a group of specialized connective tissue fibers that essentially attach a tooth to the alveolar bone within which it sits. It inserts into root cementum one side and onto alveolar b ...

and

. Nerve fibers never enters the

. Nerve-related signaling molecules, such as

Glial cell Glia, also called glial cells (gliocytes) or neuroglia, are non-neuronal cells in the central nervous system (brain and spinal cord) and the peripheral nervous system that do not produce electrical impulses. They maintain homeostasis, form myel ...

line-derived growth factor, Neurotrophin and

semaphorin Semaphorins are a class of secreted and membrane proteins that were originally identified as axonal growth cone guidance molecules. They primarily act as short-range inhibitory signals and signal through multimeric receptor complexes. Semaphorins ...

g are among the few which have been studied during the tooth development process. Of which, the verve-related signaling molecules seems to show a trend that suggest an early implication of innervation of tooth development. Similar to how many molecules are able to stimulate axonal growth or migration, various molecules are also within the bounds of possibility of being involved in the initial innervation of the tooth germ.

Odontoblast Differentiation

It is paramount to understand how

differentiate from ectomesenchymal cells to allow comprehension and explanation of normal development and to be able to affect their recruitment when needed to start repairing the

. Growth factors in the cells of the inner enamel epithelium and expressions of signaling molecules bring about the differentiation of

through normal development of the dental papilla. Exhibiting a central nucleus and few organelles, the dental papilla cells are small and undifferentiated. At this stage, the cells are separated by an acellular zone, that consist of some fine

collagen fibrils Collagen () is the main structural protein in the extracellular matrix found in the body's various connective tissues. As the main component of connective tissue, it is the most abundant protein in mammals, making up from 25% to 35% of the whole ...

, from the inner enamel epithelium. Changes will also start occurring in the adjacent dental papilla, very quickly after reversed polarity of the cells of the inner enamel epithelium. To contain increasing amounts of protein-synthesizing organelles,

s as their cytoplasm ( the liquid inside a cell but outside the nucleus) increases in volume after the ectomesenchymal cells beside the acellular zone rapidly enlarge and elongate to become preodontoblasts. When the

s differentiate and increase in size to occupy the acellular zone between the dental papilla and the inner enamel epithelium, the zone slowly is removed. With their nuclei positioned away from the inner enamel epithelium, these newly differentiated cells are distinguished by being highly polarized.

References

*Cate, A.R. Ten. Oral Histology: development, structure, and function. 5th ed. 1998. . {{Authority control Parts of tooth