The olfactory epithelium is a specialized

epithelial Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercellula ...

tissue inside the

nasal cavity The nasal cavity is a large, air-filled space above and behind the nose in the middle of the face. The nasal septum divides the cavity into two cavities, also known as fossae. Each cavity is the continuation of one of the two nostrils. The nasal c ...

that is involved in smell. In humans, it measures 9 cm² and lies on the roof of the nasal cavity about 7 cm above and behind the nostrils. The olfactory epithelium is the part of the

olfactory system The olfactory system, or sense of smell, is the sensory system used for smelling (olfaction). Olfaction is one of the special senses, that have directly associated specific organs. Most mammals and reptiles have a main olfactory system and an ac ...

directly responsible for detecting

odor An odor (American English) or odour (English in the Commonwealth of Nations, Commonwealth English; American and British English spelling differences#-our, -or, see spelling differences) is caused by one or more volatilized chemical compounds ...

Structure

Olfactory epithelium consists of four distinct cell types: *

Olfactory sensory neurons An olfactory receptor neuron (ORN), also called an olfactory sensory neuron (OSN), is a sensory neuron within the olfactory system. Structure Humans have between 10 and 20 million olfactory receptor neurons (ORNs). In vertebrates, ORNs are ...

* Supporting cells * Basal cells * Brush cells

Olfactory sensory neurons

The

olfactory receptor neuron An olfactory receptor neuron (ORN), also called an olfactory sensory neuron (OSN), is a sensory neuron within the olfactory system. Structure Humans have between 10 and 20 million olfactory receptor neurons (ORNs). In vertebrates, ORNs are b ...

s are sensory neurons of the olfactory epithelium. They are

bipolar neuron A bipolar neuron, or bipolar cell, is a type of neuron that has two extensions (one axon and one dendrite). Many bipolar cells are specialized sensory neurons for the transmission of sense. As such, they are part of the sensory pathways for smell ...

s and their apical poles express odorant receptors on non-motile cilia at the ends of the dendritic knob, which extend out into the airspace to interact with odorants. Odorant receptors bind odorants in the airspace, which are made soluble by the serous secretions from

olfactory glands Olfactory glands, also known as Bowman's glands, are a type of nasal gland situated in the olfactory mucosa, beneath the olfactory epithelium, in the lamina propria, a connective tissue also containing fibroblasts, blood vessels and bundles of fin ...

located in the lamina propria of the mucosa.Ross, MH, ''Histology: A Text and Atlas'', 5th Edition. Philadelphia: Lippincott, Williams and Wilkins, 2006. page 616. The axons of the olfactory sensory neurons congregate to form the

olfactory nerve The olfactory nerve, also known as the first cranial nerve, cranial nerve I, or simply CN I, is a cranial nerve that contains sensory nerve fibers relating to the sense of smell. The afferent nerve fibers of the olfactory receptor neurons tr ...

(CN I). Once the axons pass through the

cribriform plate In mammalian anatomy, the cribriform plate (Latin for lit. ''sieve-shaped''), horizontal lamina or lamina cribrosa is part of the ethmoid bone. It is received into the ethmoidal notch of the frontal bone and roofs in the nasal cavities. It supp ...

, they terminate and synapse with the dendrites of mitral cells in the

glomeruli ''Glomerulus'' () is a common term used in anatomy to describe globular structures of entwined vessels, fibers, or neurons. ''Glomerulus'' is the diminutive of the Latin ''glomus'', meaning "ball of yarn". ''Glomerulus'' may refer to: * the filter ...

of the

olfactory bulb The olfactory bulb (Latin: ''bulbus olfactorius'') is a grey matter, neural structure of the vertebrate forebrain involved in olfaction, the sense of odor, smell. It sends olfactory information to be further processed in the amygdala, the orbitof ...

Supporting cells

Analogous to neural

glial cells 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 ...

, the supporting cells are non-neural cells in the olfactory epithelium that are located in the apical layer of the pseudostratified ciliated columnar epithelium. There are two types of supporting cells in the olfactory epithelium:

sustentacular cell A sustentacular cell is a type of cell primarily associated with structural support, they can be found in various tissues. * Sustentacular cells of the olfactory epithelium (also called supporting cells) have been shown to be involved in the phag ...

s and microvillar cells. The sustentacular cells function as metabolic and physical support for the olfactory epithelium. Microvillar cells are another class of supporting cells that are morphologically and biochemically distinct from the sustentacular cells, and arise from a basal cell population that expresses the

c-KIT Proto-oncogene c-KIT is the gene encoding the receptor tyrosine kinase protein known as tyrosine-protein kinase KIT, CD117 (cluster of differentiation 117) or mast/stem cell growth factor receptor (SCFR). Multiple transcript variants encoding diff ...

cell surface protein.

Basal cells

Resting on or near the

basal lamina The basal lamina is a layer of extracellular matrix secreted by the epithelial cells, on which the epithelium sits. It is often incorrectly referred to as the basement membrane, though it does constitute a portion of the basement membrane. The ba ...

of the olfactory epithelium, basal cells are stem cells capable of division and differentiation into either supporting or olfactory cells. While some of these basal cells divide rapidly, a significant proportion remain relatively quiescent and replenish olfactory epithelial cells as needed. This leads to the olfactory epithelium being replaced every 6–8 weeks.

Basal cells The ''stratum basale'' (basal layer, sometimes referred to as ''stratum germinativum'') is the deepest layer of the five layers of the epidermis, the external covering of skin in mammals. The ''stratum basale'' is a single layer of columnar o ...

can be divided on the basis of their cellular and histological features into two populations: the horizontal basal cells, which are slowly dividing reserve cells that express p63; and globose basal cells, which are a heterogeneous population of cells consisting of reserve cells, amplifying progenitor cells, and immediate precursor cells.

Brush cells

brush cell Respiratory epithelium, or airway epithelium, is a type of ciliated pseudostratified columnar epithelia, ciliated columnar epithelium found lining most of the respiratory tract as respiratory mucosa, where it serves to moisten and protect the a ...

is a microvilli-bearing columnar cell with its basal surface in contact with afferent nerve endings of the

trigeminal nerve In neuroanatomy, the trigeminal nerve ( lit. ''triplet'' nerve), also known as the fifth cranial nerve, cranial nerve V, or simply CN V, is a cranial nerve responsible for sensation in the face and motor functions such as biting and chewin ...

(CN V) and is specialized for transduction of general sensation.

Olfactory (Bowman's) glands

Tubuloalveolar serous secreting glands lying in the lamina propria of the

olfactory mucosa The olfactory mucosa is located in the upper region of the nasal cavity and is made up of the olfactory epithelium and the underlying lamina propria, connective tissue containing fibroblasts, blood vessels, Bowman's glands and bundles of fine ax ...

. These glands deliver a proteinaceous secretion via ducts onto the surface of the mucosa. The role of the secretions are to trap and dissolve odiferous substances for the bipolar neurons. Constant flow from the olfactory glands allows old odors to be constantly washed away.

Development

The olfactory epithelium derives from two structures during

embryonic development An embryo is an initial stage of development of a multicellular organism. In organisms that reproduce sexually, embryonic development is the part of the life cycle that begins just after fertilization of the female egg cell by the male sperm ...

: the

olfactory placode The nasal placode (or olfactory placode) gives rise to the olfactory epithelium of the nose. Two nasal placodes arise as thickened ectoderm from the frontonasal process. They give rise to the nose, the philtrum of the upper lip, and the primary pa ...

, which was long believed to be its sole origin; and

neural crest cells 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 ...

, whose contributions have been identified more recently through

fate mapping Fate mapping is a method used in developmental biology to study the embryonic origin of various adult tissues and structures. The "fate" of each cell or group of cells is mapped onto the embryo, showing which parts of the embryo will develop into ...

studies. The embryonic olfactory epithelium consists of fewer cell types than in the adult, including apical and basal

progenitor cell A progenitor cell is a Cell (biology), biological cell that can Cellular differentiation, differentiate into a specific cell type. Stem cells and progenitor cells have this ability in common. However, stem cells are less specified than progenitor ...

s, as well as immature

olfactory sensory neurons An olfactory receptor neuron (ORN), also called an olfactory sensory neuron (OSN), is a sensory neuron within the olfactory system. Structure Humans have between 10 and 20 million olfactory receptor neurons (ORNs). In vertebrates, ORNs are ...

. Early embryonic neurogenesis relies mostly on the apical cells, while later stage embryonic

neurogenesis Neurogenesis is the process by which nervous system cells, the neurons, are produced by neural stem cells (NSCs). It occurs in all species of animals except the porifera (sponges) and placozoans. Types of NSCs include neuroepithelial cells (NECs) ...

and secondary neurogenesis in adults relies on basal stem cells. The

axon An axon (from Greek ἄξων ''áxōn'', axis), or nerve fiber (or nerve fibre: see spelling differences), is a long, slender projection of a nerve cell, or neuron, in vertebrates, that typically conducts electrical impulses known as action po ...

s of the immature

olfactory sensory neuron An olfactory receptor neuron (ORN), also called an olfactory sensory neuron (OSN), is a sensory neuron within the olfactory system. Structure Humans have between 10 and 20 million olfactory receptor neurons (ORNs). In vertebrates, ORNs are b ...

s, along with a mixed population of migratory cells, including immature

olfactory ensheathing cells Olfactory ensheathing cells (OECs), also known as olfactory ensheathing glia or olfactory ensheathing glial cells, are a type of macroglia ( radial glia) found in the nervous system. They are also known as olfactory Schwann cells, because they en ...

and gonadotropin-releasing hormone neurons form a “migratory mass” that travels towards the

. At the end of the embryonic stage, the epithelium develops into a

pseudostratified columnar epithelium A pseudostratified epithelium is a type of epithelium that, though comprising only a single layer of cells, has its cell nuclei positioned in a manner suggestive of stratified epithelia. As it rarely occurs as squamous or cuboidal epithelia, ...

and begins secondary neurogenesis.

Olfactory placode

Placode A neurogenic placode is an area of thickening of the epithelium in the embryonic head ectoderm layer that gives rise to neurons and other structures of the sensory nervous system. Placodes are embryonic structures that give rise to structures such ...

s are transient, focal aggregations of

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 ...

located in the developmental region of the future

vertebrate Vertebrates () comprise all animal taxa within the subphylum Vertebrata () ( chordates with backbones), including all mammals, birds, reptiles, amphibians, and fish. Vertebrates represent the overwhelming majority of the phylum Chordata, ...

head A head is the part of an organism which usually includes the ears, brain, forehead, cheeks, chin, eyes, nose, and mouth, each of which aid in various sensory functions such as sight, hearing, smell, and taste. Some very simple animals may ...

, and give rise to

sensory organs A sense is a biological system used by an organism for sensation, the process of gathering information about the world through the detection of stimuli. (For example, in the human body, the brain which is part of the central nervous system rec ...

. Early cranial sensory placodes are marked by expression of

Six1 Homeobox protein SIX1 (Sine oculis homeobox homolog 1) is a protein that in humans is encoded by the ''SIX1'' gene. Function The vertebrate SIX genes are homologs of the Drosophila 'sine oculis' (so) gene, which is expressed primarily in the ...

, part of the Six family of transcription factors that regulate preplacodal ectoderm specification. The

forms as two thickenings of non-neural region of

embryonic 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 the o ...

. In mice, the olfactory placode derives from an anterior portion of the

neural tube In the developing chordate (including vertebrates), the neural tube is the embryonic precursor to the central nervous system, which is made up of the brain and spinal cord. The neural groove gradually deepens as the neural fold become elevated, a ...

, ~9-9.5 days into development and not long after the closure of the

neural plate The neural plate is a key developmental structure that serves as the basis for the nervous system. Cranial to the primitive node of the embryonic primitive streak, ectodermal tissue thickens and flattens to become the neural plate. The region ante ...

. Development of the olfactory placode requires the presence underlying

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 ...

-derived

mesenchymal Mesenchyme () is a type of loosely organized animal embryonic connective tissue of undifferentiated cells that give rise to most tissues, such as skin, blood or bone. The interactions between mesenchyme and epithelium help to form nearly every o ...

tissue. The specification of the olfactory placode tissue involves signaling of multiple gene networks, beginning with signals from bone morphogenetic proteins (BMP),

retinoic acid Retinoic acid (used simplified here for all-''trans''-retinoic acid) is a metabolite of vitamin A1 (all-''trans''-retinol) that mediates the functions of vitamin A1 required for growth and development. All-''trans''-retinoic acid is required in ...

(RA), and

fibroblast growth factor Fibroblast growth factors (FGF) are a family of cell signalling proteins produced by macrophages; they are involved in a wide variety of processes, most notably as crucial elements for normal development in animal cells. Any irregularities in their ...

(FGF), specifically

FGF8 Fibroblast growth factor 8 (FGF-8) is a protein that in humans is encoded by the ''FGF8'' gene. Function The protein encoded by this gene is a member of the fibroblast growth factor (FGF) family. FGF family members possess broad mitogenic and ...

. The resulting regulated downstream expression of

transcription factor In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence. The fu ...

s, such as

Pax6 Paired box protein Pax-6, also known as aniridia type II protein (AN2) or oculorhombin, is a protein that in humans is encoded by the ''PAX6'' gene. Function PAX6 is a member of the Pax gene family which is responsible for carrying the geneti ...

Dlx3 Homeobox protein DLX-3 is a protein that in humans is encoded by the ''DLX3'' gene. Function Dlx3 is a crucial regulator of hair follicle differentiation and cycling. Dlx3 transcription is mediated through Wnt, and colocalization of Dlx3 wit ...

, Sox2, and others, within the presumptive olfactory placode are crucial for sub-regionalization within the future olfactory epithelium and is responsible for the diversity of cells that compose the future epithelium. Similar to the other embryonic placodes, the olfactory placode gives rise to both neural and non-neural structures, ultimately resulting in the formation of the nasal epithelium. The specification of neural versus non-neural tissue involves signals both within the olfactory placode, and between the olfactory placode and the underlying

compartment. Continued signaling by BMP, FGF, and RA, the

morphogen A morphogen is a substance whose non-uniform distribution governs the pattern of tissue development in the process of morphogenesis or pattern formation, one of the core processes of developmental biology, establishing positions of the various ...

s that initially induced placode formation, collectively coordinate the patterning of olfactory placode tissue into the future distinct cell types that make up the olfactory epithelium. The cell types derived from the olfactory placode include: * Neural:

LHRH Gonadotropin-releasing hormone (GnRH) is a releasing hormone responsible for the release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from the anterior pituitary. GnRH is a tropic peptide hormone synthesized and released ...

-secreting neurons, and

ganglion cell {{stack, A ganglion cell is a cell found in a ganglion. Examples of ganglion cells include: * Retinal ganglion cell (RGC) found in the ganglion cell layer of the retina * Cells that reside in the adrenal medulla, where they are involved in the ...

s * Non-neuronal: basal cells, olfactory supporting cells,

ciliated The cilium, plural cilia (), is a membrane-bound organelle found on most types of eukaryotic cell, and certain microorganisms known as ciliates. Cilia are absent in bacteria and archaea. The cilium has the shape of a slender threadlike projecti ...

cells, Bowman’s glands,

Schwann cell Schwann cells or neurolemmocytes (named after German physiologist Theodor Schwann) are the principal glia of the peripheral nervous system (PNS). Glial cells function to support neurons and in the PNS, also include satellite cells, olfactory ensh ...

submucosal glands Submucosal glands can refer to various racemose exocrine glands of the mucous type. These glands secrete mucus to facilitate the movement of particles along the body's various tubes, such as the throat and intestines. The mucosa is the lining of th ...

, and

s However, there is significant evidence for an additional

-origin for many of these cell types as well.

Olfactory sensory neuron development

Olfactory Sensory Neurons innervating Olfactory Glomeruli

Olfaction The sense of smell, or olfaction, is the special sense through which smells (or odors) are perceived. The sense of smell has many functions, including detecting desirable foods, hazards, and pheromones, and plays a role in taste. In humans, it ...

results from the proper development and interaction of the two components of the primary olfactory pathway: the olfactory epithelium and the

. The olfactory epithelium contains

, whose

innervate A nerve is an enclosed, cable-like bundle of nerve fibers (called axons) in the peripheral nervous system. A nerve transmits electrical impulses. It is the basic unit of the peripheral nervous system. A nerve provides a common pathway for the e ...

the olfactory bulb. In order for olfactory sensory neurons to function properly, they must express

odorant receptors Olfactory receptors (ORs), also known as odorant receptors, are chemoreceptors expressed in the cell membranes of olfactory receptor neurons and are responsible for the detection of odorants (for example, compounds that have an odor) which give ri ...

and the proper transduction proteins on non-motile cilia that extend from the dendritic knob in addition to projecting their axons to the olfactory bulb. The cells of the olfactory epithelium, including olfactory sensory neurons, begin to differentiate soon after the induction of the

. Once the olfactory sensory neurons differentiate, they express odorant receptors, which transduce

odorant An aroma compound, also known as an odorant, aroma, fragrance or flavoring, is a chemical compound that has a smell or odor. For an individual chemical or class of chemical compounds to impart a smell or fragrance, it must be sufficiently vol ...

information from the environment to the

central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all par ...

and aids in the development of the odorant map. The differentiated olfactory sensory neurons extend pioneering axons, which follow guidance cues released by the underlying

mesenchyme Mesenchyme () is a type of loosely organized animal embryonic connective tissue of undifferentiated cells that give rise to most tissues, such as skin, blood or bone. The interactions between mesenchyme and epithelium help to form nearly every o ...

, as well as other chemotrophic cues released from the

telencephalon The cerebrum, telencephalon or endbrain is the largest part of the brain containing the cerebral cortex (of the two cerebral hemispheres), as well as several subcortical structures, including the hippocampus, basal ganglia, and olfactory bulb. In ...

. As development of the olfactory pathway progresses, more axons innervate the olfactory bulb, which develops from the rostral-most region of telencephalon. The organization and subsequent processing of odorant information is possible due to the convergence of olfactory sensory neuron axons expressing the same odorant receptors onto the same

glomerulus ''Glomerulus'' () is a common term used in anatomy to describe globular structures of entwined vessels, fibers, or neurons. ''Glomerulus'' is the diminutive of the Latin ''glomus'', meaning "ball of yarn". ''Glomerulus'' may refer to: * the filter ...

at the olfactory bulb.

Clinical significance

The olfactory epithelium can be damaged by inhalation of toxic fumes, physical injury to the interior of the nose, and possibly by the use of some nasal sprays. Because of its regenerative capacity, damage to the olfactory epithelium can be temporary but in extreme cases, injury can be permanent, leading to

anosmia Anosmia, also known as smell blindness, is the loss of the ability to detect one or more smells. Anosmia may be temporary or permanent. It differs from hyposmia, which is a decreased sensitivity to some or all smells. Anosmia can be due to a nu ...

Additional images

Image:Riechschleimhaut.svg, Composition of the Olfactory receptor neuron (captions in German) Image:Olfactorisch epitheel varken olfactory epithelium pig.jpg, olfactory epithelium pig

References

External links

Embryonic origin of the olfactory sensory system: fate map, lineage analysis and specification of the avian olfactory placode
an

* {{DEFAULTSORT:Olfactory Epithelium Olfactory system