Mesenchyme () is a type of loosely organized animal

embryonic Embryonic may refer to: *Of or relating to an embryo * ''Embryonic'' (album), a 2009 studio album by the Flaming Lips *''Embryonics ''Embryonics'' is a double-CD compilation of tracks by the Australian progressive metal band, Alchemist. It w ...

connective tissue Connective tissue is one of the four primary types of animal tissue, along with epithelial tissue, muscle tissue, and nervous tissue. It develops from the mesenchyme derived from the mesoderm the middle embryonic germ layer. Connective tiss ...

of undifferentiated cells that give rise to most tissues, such as

skin Skin is the layer of usually soft, flexible outer tissue covering the body of a vertebrate animal, with three main functions: protection, regulation, and sensation. Other cuticle, animal coverings, such as the arthropod exoskeleton, have diffe ...

blood Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells. Blood in the c ...

bone A bone is a Stiffness, rigid Organ (biology), organ that constitutes part of the skeleton in most vertebrate animals. Bones protect the various other organs of the body, produce red blood cell, red and white blood cells, store minerals, provid ...

. The interactions between mesenchyme and

epithelium 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 intercellul ...

help to form nearly every organ in the developing embryo.

Vertebrates

Structure

Mesenchyme is characterized morphologically by a prominent

ground substance Ground substance is an amorphous gel-like substance in the extracellular space that contains all components of the extracellular matrix (ECM) except for fibrous materials such as collagen and elastin. Ground substance is active in the development, m ...

matrix Matrix most commonly refers to: * ''The Matrix'' (franchise), an American media franchise ** ''The Matrix'', a 1999 science-fiction action film ** "The Matrix", a fictional setting, a virtual reality environment, within ''The Matrix'' (franchis ...

containing a loose aggregate of

reticular fiber Reticular fibers, reticular fibres or reticulin is a type of fiber in connective tissue composed of type III collagen secreted by reticular cells. Reticular fibers crosslink to form a fine meshwork (reticulin). This network acts as a supportin ...

s and unspecialized

mesenchymal stem cells Mesenchymal stem cells (MSCs) also known as mesenchymal stromal cells or medicinal signaling cells are multipotent stromal cells that can differentiate into a variety of cell types, including osteoblasts (bone cells), chondrocytes (cartilage ce ...

. Mesenchymal cells can migrate easily (in contrast to

epithelial cell 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 ...

s, which lack mobility), are organized into closely adherent sheets, and are polarized in an apical-basal orientation.

Development

The mesenchyme originates from 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 ...

. From the mesoderm, the mesenchyme appears as an embryologically primitive "soup". This "soup" exists as a combination of the mesenchymal cells plus serous fluid plus the many different tissue proteins. Serous fluid is typically stocked with the many serous elements, such as sodium and chloride. The mesenchyme develops into the tissues of the

lymphatic Lymph (from Latin, , meaning "water") is the fluid that flows through the lymphatic system, a system composed of lymph vessels (channels) and intervening lymph nodes whose function, like the venous system, is to return fluid from the tissues to ...

and

circulatory The blood circulatory system is a system of organs that includes the heart, blood vessels, and blood which is circulated throughout the entire body of a human or other vertebrate. It includes the cardiovascular system, or vascular system, tha ...

systems, as well as the musculoskeletal system. This latter system is characterized as

s throughout the body, such as

, and

cartilage Cartilage is a resilient and smooth type of connective tissue. In tetrapods, it covers and protects the ends of long bones at the joints as articular cartilage, and is a structural component of many body parts including the rib cage, the neck an ...

. A malignant

cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...

of mesenchymal cells is a type of

sarcoma A sarcoma is a malignant tumor, a type of cancer that arises from transformed cells of mesenchymal (connective tissue) origin. Connective tissue is a broad term that includes bone, cartilage, fat, vascular, or hematopoietic tissues, and sarcom ...

Epithelial to mesenchymal transition

The first emergence of mesenchyme occurs during

gastrulation Gastrulation is the stage in the early embryonic development of most animals, during which the blastula (a single-layered hollow sphere of cells), or in mammals the blastocyst is reorganized into a multilayered structure known as the gastrula. Be ...

from the

epithelial–mesenchymal transition The epithelial–mesenchymal transition (EMT) is a process by which epithelial cells lose their cell polarity and cell–cell adhesion, and gain migratory and invasive properties to become mesenchymal stem cells; these are multipotent stromal ...

(EMT) process. This transition occurs through the loss of epithelial cadherin,

tight junction Tight junctions, also known as occluding junctions or ''zonulae occludentes'' (singular, ''zonula occludens''), are multiprotein junctional complexes whose canonical function is to prevent leakage of solutes and water and seals between the epith ...

s, and

adherens junction Adherens junctions (or zonula adherens, intermediate junction, or "belt desmosome") are protein complexes that occur at cell–cell junctions, cell–matrix junctions in epithelial and endothelial tissues, usually more basal than tight junctions. ...

s on the

cell membrane The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment ( ...

s of

epithelial cells 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 ...

. The surface molecules undergo

endocytosis Endocytosis is a cellular process in which substances are brought into the cell. The material to be internalized is surrounded by an area of cell membrane, which then buds off inside the cell to form a vesicle containing the ingested material. E ...

and the

microtubule Microtubules are polymers of tubulin that form part of the cytoskeleton and provide structure and shape to eukaryotic cells. Microtubules can be as long as 50 micrometres, as wide as 23 to 27 nm and have an inner diameter between 11 an ...

cytoskeleton loses shape, enabling mesenchyme to migrate along the

extracellular matrix In biology, the extracellular matrix (ECM), also called intercellular matrix, is a three-dimensional network consisting of extracellular macromolecules and minerals, such as collagen, enzymes, glycoproteins and hydroxyapatite that provide stru ...

(ECM). Epithelial–mesenchymal transition occurs in embryonic cells that require migration through or over tissue, and can be followed with a

mesenchymal–epithelial transition A mesenchymal–epithelial transition (MET) is a reversible biological process that involves the transition from motile, multipolar or spindle-shaped mesenchymal cells to planar arrays of polarized cells called epithelia. MET is the reverse proce ...

to produce secondary epithelial tissues. Embryological mesenchymal cells express Protein S100-A4 (''S100A4'') also known as ''fibroblast-specific protein'', which is indicative of their shared properties with the migratory adult

fibroblasts A fibroblast is a type of biological cell that synthesizes the extracellular matrix and collagen, produces the structural framework ( stroma) for animal tissues, and plays a critical role in wound healing. Fibroblasts are the most common cells o ...

, and

c-Fos Protein c-Fos is a proto-oncogene that is the human homolog of the retroviral oncogene v-fos. It is encoded in humans by the ''FOS'' gene. It was first discovered in rat fibroblasts as the transforming gene of the FBJ MSV (Finkel–Biskis–Jinkin ...

, an

oncogene An oncogene is a gene that has the potential to cause cancer. In tumor cells, these genes are often mutated, or expressed at high levels.

associated with the down-regulation of epithelial cadherin. Both formation of the

primitive streak The primitive streak is a structure that forms in the early embryo in amniotes. In amphibians the equivalent structure is the blastopore. During early embryonic development, the embryonic disc becomes oval shaped, and then pear-shaped with the ...

and mesenchymal tissue is dependent on the Wnt/β-catenin pathway. Specific markers of mesenchymal tissue include the additional expression of ECM factors such as

fibronectin Fibronectin is a high- molecular weight (~500-~600 kDa) glycoprotein of the extracellular matrix that binds to membrane-spanning receptor proteins called integrins. Fibronectin also binds to other extracellular matrix proteins such as collage ...

and

vitronectin Vitronectin (VTN or VN) is a glycoprotein of the hemopexin family which is abundantly found in serum, the extracellular matrix and bone. In humans it is encoded by the ''VTN'' gene. Vitronectin binds to integrin alpha-V beta-3 and thus promotes c ...

Implantation

The first cells of the embryo to undergo EMT and form mesenchyme are the extra-embryonic cells of the

trophectoderm The trophoblast (from Greek : to feed; and : germinator) is the outer layer of cells of the blastocyst. Trophoblasts are present four days after fertilization in humans. They provide nutrients to the embryo and develop into a large part of the ...

. These migrate from the body of the

blastocyst The blastocyst is a structure formed in the early embryonic development of mammals. It possesses an inner cell mass (ICM) also known as the ''embryoblast'' which subsequently forms the embryo, and an outer layer of trophoblast cells called the t ...

into the

endometrial The endometrium is the inner epithelial layer, along with its mucous membrane, of the mammalian uterus. It has a basal layer and a functional layer: the basal layer contains stem cells which regenerate the functional layer. The functional layer ...

layer of the

uterus The uterus (from Latin ''uterus'', plural ''uteri'') or womb () is the organ in the reproductive system of most female mammals, including humans that accommodates the embryonic and fetal development of one or more embryos until birth. The uter ...

in order to contribute to the formation of the anchored

placenta The placenta is a temporary embryonic and later fetal organ that begins developing from the blastocyst shortly after implantation. It plays critical roles in facilitating nutrient, gas and waste exchange between the physically separate mater ...

Primary mesenchyme

Primary mesenchyme is the first embryonic mesenchymal tissue to emerge, and it is produced from EMT in

epiblast In amniote embryonic development, the epiblast (also known as the primitive ectoderm) is one of two distinct cell layers arising from the inner cell mass in the mammalian blastocyst, or from the blastula in reptiles and birds, the other layer is t ...

cells. In the

, it is induced by the

through

Wnt signaling The Wnt signaling pathways are a group of signal transduction pathways which begin with proteins that pass signals into a cell through cell surface receptors. The name Wnt is a portmanteau created from the names Wingless and Int-1. Wnt signaling ...

, and produces

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 ...

and

from a transitory tissue called mesendoderm during the process of

. The formation of primary mesenchyme depends on the expression of

WNT3 Proto-oncogene protein Wnt-3 is a protein that in humans is encoded by the ''WNT3'' gene In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' ...

. Other deficiencies in signaling pathways, such as in

Nodal Nodal homolog is a secretory protein that in humans is encoded by the ''NODAL'' gene which is located on chromosome 10q22.1. It belongs to the transforming growth factor beta superfamily (TGF-β superfamily). Like many other members of this superf ...

(a TGF-beta protein), will lead to defective

formation. The tissue layers formed from the primitive streak invaginate together into the embryo and the induced

will ingress and form the

. Mesodermal tissue will continue to differentiate and/or migrate throughout the embryo to ultimately form most

layers of the body.

Neural mesenchyme

Embryological mesenchyme is particularly transitory and soon differentiates after migration. Neural mesenchyme forms soon after primary mesenchyme formation. The interaction with

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 ...

and somite-forming morphogenic factors cause some primary mesenchyme to form neural mesenchyme, or

paraxial mesoderm Paraxial mesoderm, also known as presomitic or somitic mesoderm is the area of mesoderm in the neurulating embryo that flanks and forms simultaneously with the neural tube. The cells of this region give rise to somites, blocks of tissue running ...

, and contribute to

somite The somites (outdated term: primitive segments) are a set of bilaterally paired blocks of paraxial mesoderm that form in the embryonic stage of somitogenesis, along the head-to-tail axis in segmented animals. In vertebrates, somites subdivide in ...

formation. Neural mesenchyme soon undergoes a

under the influence of

WNT6 Wingless-type MMTV integration site family, member 6, also known as WNT6, is a human gene. The WNT gene family consists of structurally related genes that encode secreted signaling proteins. These proteins have been implicated in oncogenesis and ...

produced by

to form

somites The somites (outdated term: primitive segments) are a set of bilaterally paired blocks of paraxial mesoderm that form in the embryonic stage of somitogenesis, along the head-to-tail axis in segmented animals. In vertebrates, somites subdivide i ...

. These structures will undergo a secondary EMT as the

tissue migrates later in development to form structural

such as

and

skeletal muscle Skeletal muscles (commonly referred to as muscles) are organs of the vertebrate muscular system and typically are attached by tendons to bones of a skeleton. The muscle cells of skeletal muscles are much longer than in the other types of muscl ...

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 ...

(NCCs) form from

neuroectoderm Neuroectoderm (or neural ectoderm or neural tube epithelium) consists of cells derived from ectoderm. Formation of the neuroectoderm is first step in the development of the nervous system. The neuroectoderm receives bone morphogenetic protein-inh ...

, instead of the primary mesenchyme, from morphogenic signals of the

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 ...

. The EMT occurs as a result of

, the influence of

Sox genes ''SOX'' genes ('' SRY''-related HMG-box genes) encode a family of transcription factors that bind to the minor groove in DNA, and belong to a super-family of genes characterized by a homologous sequence called the HMG-box (for high mobility ...

and the loss of

E-cadherin Cadherin-1 or Epithelial cadherin (E-cadherin), (not to be confused with the APC/C activator protein CDH1) is a protein that in humans is encoded by the ''CDH1'' gene. Mutations are correlated with gastric, breast, colorectal, thyroid, and ovarian ...

from the cell surface. NCCs additionally require the repression of

N-cadherin Cadherin-2 also known as Neural cadherin (N-cadherin), is a protein that in humans is encoded by the ''CDH2'' gene. CDH2 has also been designated as CD325 (cluster of differentiation 325). Cadherin-2 is a transmembrane protein expressed in multipl ...

, and

neural cell adhesion molecule Neural cell adhesion molecule (NCAM), also called CD56, is a homophilic binding glycoprotein expressed on the surface of neurons, glia and skeletal muscle. Although CD56 is often considered a marker of neural lineage commitment due to its discover ...

. NCCs ingress into the embryo from the epithelial neuroectodermal layer and migrate throughout the body in order form multiple

peripheral nervous system The peripheral nervous system (PNS) is one of two components that make up the nervous system of bilateral animals, with the other part being the central nervous system (CNS). The PNS consists of nerves and ganglia, which lie outside the brain ...

(PNS) cells and

melanocytes Melanocytes are melanin-producing neural crest-derived cells located in the bottom layer (the stratum basale) of the skin's epidermis, the middle layer of the eye (the uvea), the inner ear, vaginal epithelium, meninges, bones, and heart. ...

. Migration of NCCs is primarily induced by BMP signaling and its inhibitor,

Noggin Noggin may refer to: General * Noggin or gill (volume), a unit of volume * Noggin (cup), a small cup * Noggin, slang for head A head is the part of an organism which usually includes the ears, brain, forehead, cheeks, chin, eyes, nose, an ...

Invertebrates

In some

invertebrate Invertebrates are a paraphyletic group of animals that neither possess nor develop a vertebral column (commonly known as a ''backbone'' or ''spine''), derived from the notochord. This is a grouping including all animals apart from the chordate ...

s, e.g.,

Porifera Sponges, the members of the phylum Porifera (; meaning 'pore bearer'), are a basal animal clade as a sister of the diploblasts. They are multicellular organisms that have bodies full of pores and channels allowing water to circulate through th ...

Cnidaria Cnidaria () is a phylum under kingdom Animalia containing over 11,000 species of aquatic animals found both in freshwater and marine environments, predominantly the latter. Their distinguishing feature is cnidocytes, specialized cells that th ...

Ctenophora Ctenophora (; ctenophore ; ) comprise a phylum of marine invertebrates, commonly known as comb jellies, that inhabit sea waters worldwide. They are notable for the groups of cilia they use for swimming (commonly referred to as "combs"), an ...

and some

triploblast Triploblasty is a condition of the gastrula in which there are three primary germ layers: the ectoderm, mesoderm, and endoderm. Germ cells are set aside in the embryo at the blastula stage, which are incorporated into the gonads during organogenes ...

s (the

acoelomates The coelom (or celom) is the main body cavity in most animals and is positioned inside the Body (biology), body to surround and contain the digestive tract and other Organ (biology), organs. In some animals, it is lined with mesothelium. In other ...

), mesenchyme refers to a more-or-less solid but loosely organized tissue consisting of a gel matrix (the

mesoglea Mesoglea refers to the extracellular matrix found in cnidarians like coral or jellyfish that functions as a hydrostatic skeleton. It is related to but distinct from mesohyl, which generally refers to extracellular material found in sponges. Descr ...

) with various cellular and fibrous inclusions, located between the

epidermis The epidermis is the outermost of the three layers that comprise the skin, the inner layers being the dermis and hypodermis. The epidermis layer provides a barrier to infection from environmental pathogens and regulates the amount of water rele ...

and the

gastrodermis The gastrodermis is the inner layer of cells that serves as a lining membrane of the gastrovascular cavity of Cnidarians. The term is also used for the analogous inner epithelial layer of Ctenophore Ctenophora (; ctenophore ; ) comprise a ph ...

(non-triploblast animals usually are considered to lack "connective" tissue). In some cases, the mesoglea is noncellular. * In

sponge Sponges, the members of the phylum Porifera (; meaning 'pore bearer'), are a basal animal clade as a sister of the diploblasts. They are multicellular organisms that have bodies full of pores and channels allowing water to circulate through t ...

s, the mesenchyme is called

mesohyl The mesohyl, formerly known as mesenchyme or as mesoglea, is the gelatinous matrix within a sponge. It fills the space between the external pinacoderm and the internal choanoderm. The mesohyl resembles a type of connective tissue and contains sev ...

. * In diploblasts (Cnidaria and Ctenophora), the mesenchyme is fully ectodermally derived. This kind of mesenchyme is called ectomesodermal, and is not considered true

. * In triploblastic acoelomates (such as

flatworm The flatworms, flat worms, Platyhelminthes, or platyhelminths (from the Greek πλατύ, ''platy'', meaning "flat" and ἕλμινς (root: ἑλμινθ-), ''helminth-'', meaning "worm") are a phylum of relatively simple bilaterian, unsegment ...

s), the term

parenchyma Parenchyma () is the bulk of functional substance in an animal organ or structure such as a tumour. In zoology it is the name for the tissue that fills the interior of flatworms. Etymology The term ''parenchyma'' is New Latin from the word π ...

is sometimes used for the middle (mesenchymal) layer, in which the dense layer includes tissues derived from both ectoderm, and entomesoderm (true mesoderm, derived from

entoderm 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 ga ...

). When cellular material is sparse or densely packed, as in cnidarians, the mesenchyme may sometimes be called

collenchyma The ground tissue of plants includes all tissues that are neither dermal nor vascular. It can be divided into three types based on the nature of the cell walls. # Parenchyma cells have thin primary walls and usually remain alive after they bec ...

, or parenchyma in flatworms. When no cellular material is present as in

Hydrozoa Hydrozoa (hydrozoans; ) are a taxonomic class of individually very small, predatory animals, some solitary and some colonial, most of which inhabit saline water. The colonies of the colonial species can be large, and in some cases the specializ ...

), the layer is properly called

. In some

colonial Colonial or The Colonial may refer to: * Colonial, of, relating to, or characteristic of a colony or colony (biology) Architecture * American colonial architecture * French Colonial * Spanish Colonial architecture Automobiles * Colonial (1920 au ...

cnidarians, the mesenchyme is perforated by gastrovascular channels continuous among colony members. This entire matrix of common basal material is called

coenenchyme Coenenchyme is the common tissue that surrounds and links the polyps in octocorals. It consists of mesoglea penetrated by tubes (''solenia'') and canals of the gastrodermis and contains sclerites, microscopic mineralised spicules of silica or of ca ...

References

* {{Authority control Connective tissue