Intermediate mesoderm or intermediate mesenchyme is a narrow section of 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 ...

(one of the three primary

germ layer A germ layer is a primary layer of cell (biology), cells that forms during embryonic development. The three germ layers in vertebrates are particularly pronounced; however, all eumetazoans (animals that are sister taxa to the sponges) produce tw ...

s) located between the

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 the lateral plate of the developing

embryo An embryo ( ) is the initial stage of development for 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 sp ...

. The intermediate mesoderm develops into vital parts of the

urogenital system The genitourinary system, or urogenital system, are the sex organs of the reproductive system and the organ (biology), organs of the urinary system. These are grouped together because of their proximity to each other, Development of the urinary a ...

(

kidney In humans, the kidneys are two reddish-brown bean-shaped blood-filtering organ (anatomy), organs that are a multilobar, multipapillary form of mammalian kidneys, usually without signs of external lobulation. They are located on the left and rig ...

gonad A gonad, sex gland, or reproductive gland is a Heterocrine gland, mixed gland and sex organ that produces the gametes and sex hormones of an organism. Female reproductive cells are egg cells, and male reproductive cells are sperm. The male gon ...

s and respective tracts).

Early formation

Factors regulating the formation of the intermediate mesoderm are not fully understood. It is believed that bone morphogenic proteins, or BMPs, specify regions of growth along the dorsal-ventral axis of the mesoderm and plays a central role in formation of the intermediate mesoderm. Vg1/ Nodal signalling is an identified regulator of intermediate mesoderm formation acting through BMP signalling. Excess Vg1/Nodal signalling during early

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 two-layered or three-layered embryo known as ...

stages results in expansion of the intermediate mesoderm at the expense of the adjacent paraxial mesoderm, whereas inhibition of Vg1/Nodal signalling represses intermediate mesoderm formation. A link has been established between Vg1/Nodal signalling and BMP signalling, whereby Vg1/Nodal signalling regulates intermediate mesoderm formation by modulating the growth-inducing effects of BMP signalling. Other necessary markers of intermediate mesoderm induction include the odd-skipped related gene ('' Osr1'') and paired-box-2 gene ('' Pax2'') which require intermediate levels of BMP signalling to activate Markers of early intermediate mesoderm formation are often not exclusive to the intermediate mesoderm. This can be seen in early stages of intermediate mesoderm differentiation where higher levels of BMP stimulate growth of lateral plate tissue, whilst lower concentrations lead to paraxial mesoderm and

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

formation. Osr1, which encodes a zinc-finger DNA-binding protein, and LIM-type homeobox gene ('' Lhx1'') expression overlaps the intermediate mesoderm as well as the lateral plate. ''Osr1'' has expression domains encompassing the entire length of the anterior-posterior (AP) axis from the first somites. It is not until the 4th-8th somite stage that markers with greater specificity to the intermediate mesoderm are identified including ''Pax2/8'' genes activated from the 6th somite (Bouchard, 2002). ''Lhx1'' expression also becomes more restricted to the intermediate mesoderm. Genetic analyses in animal studies show that ''Lhx1'', ''Osr1'' and ''Pax2/8'' signalling are all critical in specification of the intermediate mesoderm into its early derivatives.

Derived organs and tissues

As development proceeds, the intermediate mesoderm differentiates sequentially along the anterior-posterior axis into three successive stages of the early

mammalian A mammal () is a vertebrate animal of the Class (biology), class Mammalia (). Mammals are characterised by the presence of milk-producing mammary glands for feeding their young, a broad neocortex region of the brain, fur or hair, and three ...

and avian urogenital system, named

pronephros Pronephros is the most basic of the three excretory organs that develop in vertebrates, corresponding to the first stage of kidney development. It is succeeded by the mesonephros, which in fish and amphibians remains as the adult kidney. In am ...

mesonephros The mesonephros () is one of three excretory system, excretory organs that develop in vertebrates. It serves as the main excretory organ of aquatic vertebrates and as a temporary kidney in reptiles, birds, and mammals. The mesonephros is included ...

and

metanephros Kidney development, or nephrogenesis, describes the embryologic origins of the kidney, a major organ in the urinary system. This article covers a 3 part developmental process that is observed in most reptiles, birds and mammals, including humans. ...

respectively (

anamniote The anamniotes are an paraphyly, informal group of craniates comprising all fish and amphibians, which lay their eggs in aquatic environments. They are distinguished from the amniotes (reptiles, birds and mammals), which can reproduce on dry land ...

embryos form only a pronephros and mesonephros). The intermediate mesoderm will eventually develop into the kidney and parts of both male and female reproductive systems.

Kidneys

Early

structures include the pronephros and mesonephros, whose complexity, size and duration can vary greatly between

vertebrate Vertebrates () are animals with a vertebral column (backbone or spine), and a cranium, or skull. The vertebral column surrounds and protects the spinal cord, while the cranium protects the brain. The vertebrates make up the subphylum Vertebra ...

species. The adult kidney, also referred to as the ''metanephric kidney'', forms at the posterior end of the intermediate mesoderm after the degeneration of previous, less complex kidney structures.

Pronephros

During early development (approximately day 22 in

humans Humans (''Homo sapiens'') or modern humans are the most common and widespread species of primate, and the last surviving species of the genus ''Homo''. They are Hominidae, great apes characterized by their Prehistory of nakedness and clothing ...

), the pronephric duct forms from the intermediate mesoderm,

ventral Standard anatomical terms of location are used to describe unambiguously the anatomy of humans and other animals. The terms, typically derived from Latin or Greek roots, describe something in its standard anatomical position. This position prov ...

to the

anterior Standard anatomical terms of location are used to describe unambiguously the anatomy of humans and other animals. The terms, typically derived from Latin or Greek roots, describe something in its standard anatomical position. This position pro ...

somites. The cells of the pronephric duct migrate

caudally Standard anatomical terms of location are used to describe unambiguously the anatomy of humans and other animals. The terms, typically derived from Latin or Greek roots, describe something in its standard anatomical position. This position provi ...

whilst inducing adjacent

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 ever ...

to form the tubules of the initial kidney-like structure called the pronephros. This process is regulated by Pax2/8 markers. The pronephros is active in adult forms of some primitive fish and acts as the primary

excretory system The excretory system is a passive biological system that removes excess, unnecessary materials from the body fluids of an organism, so as to help maintain internal chemical homeostasis and prevent damage to the body. The dual function of excret ...

in amphibious larvae and embryonic forms of more advanced

fish A fish (: fish or fishes) is an aquatic animal, aquatic, Anamniotes, anamniotic, gill-bearing vertebrate animal with swimming fish fin, fins and craniate, a hard skull, but lacking limb (anatomy), limbs with digit (anatomy), digits. Fish can ...

. In mammals however, the pronephric tubules and the anterior portion of the pronephric duct degenerates in 3.5 weeks to be succeeded by the mesonephros, the embryonic kidney.

Mesonephros

The mesonephros is constituted of a set of new tubules formed from the

lateral Lateral is a geometric term of location which may also refer to: Biology and healthcare * Lateral (anatomy), a term of location meaning "towards the side" * Lateral cricoarytenoid muscle, an intrinsic muscle of the larynx * Lateral release ( ...

and

sides of the gonadal ridge joining the

cloaca A cloaca ( ), : cloacae ( or ), or vent, is the rear orifice that serves as the only opening for the digestive (rectum), reproductive, and urinary tracts (if present) of many vertebrate animals. All amphibians, reptiles, birds, cartilagin ...

. The mesonephros functions between the 6th and 10th weeks of embryological life of mammals as a temporary kidney, but serves as the permanent excretory organ of aquatic vertebrates. By 8 weeks post- conception, the human mesonephros reaches maximum size and begins to regress, with complete regression occurring by week 16. Despite its transiency, the mesonephros is crucial for the development of structures such as the

Wolffian duct The mesonephric duct, also known as the Wolffian duct, archinephric duct, Leydig's duct or nephric duct, is a paired organ that develops in the early stages of embryonic development in humans and other mammals. It is an important structure that p ...

(or mesonephric duct), which in turn gives rise to the

ureteric bud The ureteric bud, also known as the metanephric diverticulum, is a protrusion from the mesonephric duct during the development of the urinary and reproductive organs. It later develops into a conduit for urine drainage from the kidneys, which, in c ...

of the metanephric kidney.

Metanephros

The permanent kidney of

amniotes Amniotes are tetrapod vertebrate animals belonging to the clade Amniota, a large group that comprises the vast majority of living terrestrial and semiaquatic vertebrates. Amniotes evolved from amphibious stem tetrapod ancestors during the ...

, the metanephros, develops during the 10th week in human embryos and is formed by the reciprocal interactions of the

metanephrogenic blastema The metanephrogenic blastema or metanephric blastema (or metanephric mesenchyme, or metanephric mesoderm) is one of the two embryological structures that give rise to the kidney, the other being the ureteric bud. The metanephric blastema mostly d ...

(or metaneophrogenic mesenchyme) and the ureteric bud. Gonadal derived neurotrophic factor (GDNF) secreted by the metanephrogenic blastema activates the receptor tyrosine kinase RET, via the co-receptor GFRα1 and triggers outgrowth of Ret positive cells from the nephric duct towards the GDNF signal, promoting ureteric bud outgrowth and invasion. Once the bud invades the metanephrogenic blastema, a permissive signal in the form of Wnt proteins is activated and stimulates the

condensation Condensation is the change of the state of matter from the gas phase into the liquid phase, and is the reverse of vaporization. The word most often refers to the water cycle. It can also be defined as the change in the state of water vapor ...

of metanephric mesenchymal cells around the ureteric bud tips, beginning the polarisation of the blastema to generate the

epithelial Epithelium or epithelial tissue is a thin, continuous, protective layer of cells with little extracellular matrix. An example is the epidermis, the outermost layer of the skin. Epithelial ( mesothelial) tissues line the outer surfaces of man ...

cells of parts of the

nephron The nephron is the minute or microscopic structural and functional unit of the kidney. It is composed of a renal corpuscle and a renal tubule. The renal corpuscle consists of a tuft of capillaries called a glomerulus and a cup-shaped structu ...

: the

proximal Standard anatomical terms of location are used to describe unambiguously the anatomy of humans and other animals. The terms, typically derived from Latin or Greek roots, describe something in its standard anatomical position. This position prov ...

tubules, loops of Henle and the distal convoluted tubules. The ureteric bud secretes FGF2 (fibroblast growth factor 2) and BMP7 (bone morphogenic protein 7) to prevent

apoptosis Apoptosis (from ) is a form of programmed cell death that occurs in multicellular organisms and in some eukaryotic, single-celled microorganisms such as yeast. Biochemistry, Biochemical events lead to characteristic cell changes (Morphology (biol ...

in the kidney mesenchyme. Condensing mesenchyme then secretes

paracrine In cellular biology, paracrine signaling is a form of cell signaling, a type of cellular communication (biology), cellular communication in which a Cell (biology), cell produces a signal to induce changes in nearby cells, altering the behaviour of ...

factors that mediate branching of the ureteric bud to give rise to the

ureter The ureters are tubes composed of smooth muscle that transport urine from the kidneys to the urinary bladder. In an adult human, the ureters typically measure 20 to 30 centimeters in length and about 3 to 4 millimeters in diameter. They are lin ...

and

collecting duct The collecting duct system of the kidney consists of a series of tubules and ducts that physically connect nephrons to a minor calyx or directly to the renal pelvis. The collecting duct participates in electrolyte and fluid balance through rea ...

of the adult kidney.

Related malformations and disorders

Wilm's tumor

Wilms' tumor Wilms' tumor or Wilms tumor, also known as nephroblastoma, is a cancer of the kidneys that typically occurs in children (rarely in adults), and occurs most commonly as a renal tumor in child patients. It is named after Max Wilms, the German sur ...

(WT), also known as nephroblastoma, is an embryonic

tumor A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...

originating from metanephric blastemal cells that are incapable of completing the mesenchymal-epithelial transition (MET), a crucial process during kidney differentiation involving the transition from a multipolar, spindle-shaped mesenchymal cell to a planar assembly of polarized epithelial cells. As a consequence, WTs have a triphasic histology composed of three morphogenically distinct cell types: undifferentiated blastemal cells,

cells, and

stromal Stromal cells, or mesenchymal stromal cells, are differentiating cells found in abundance within bone marrow but can also be seen all around the body. Stromal cells can become connective tissue cells of any organ, for example in the uterine muco ...

cells. The Wnt/ βcatenin signalling pathway is crucial for initiating MET, where specifically the

WNT4 WNT4 is a secreted protein that, in humans, is encoded by the ''WNT4'' gene, found on chromosome 1. It promotes female sex development and represses male sex development. Loss of function may have consequences, such as female to male sex revers ...

protein is required for induction of epithelial renal vesicles and the transition from mesenchymal to epithelial cells. WTs are often a result of a genetic deletions or inactivating

mutation In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, ...

s in

WT1 Wilms tumor protein (WT33) is a protein that in humans is encoded by the ''WT1'' gene on chromosome 11p. Function This gene encodes a transcription factor that contains four zinc finger motifs at the C-terminus and a proline / glutamine-rich ...

(Wilms tumor 1), which subsequently inhibits Wnt/βcatenin signalling and prevents MET progression.

Persistent Müllerian duct syndrome

Persistent Müllerian duct syndrome Persistent Müllerian duct syndrome (PMDS) is the presence of Müllerian duct derivatives (fallopian tubes, uterus, and/or the upper part of the vagina) in what would be considered a genetically and otherwise physically normal male. In humans, ...

(PMDS) is a congenital disorder of

male Male (Planet symbols, symbol: ♂) is the sex of an organism that produces the gamete (sex cell) known as sperm, which fuses with the larger female gamete, or Egg cell, ovum, in the process of fertilisation. A male organism cannot sexual repro ...

sexual development and is a form of

pseudohermaphroditism Pseudohermaphroditism is an outdated term for when an individual's gonads were mismatched with their internal reproductive system and/or external genitalia. The term was contrasted with "true hermaphroditism" (now known as ovotesticular syndrome), ...

. Males with PMDS retain normal male reproductive organs and external

genitalia A sex organ, also known as a reproductive organ, is a part of an organism that is involved in sexual reproduction. Sex organs constitute the primary sex characteristics of an organism. Sex organs are responsible for producing and transporting ...

, but also possess internal female reproductive organs such as the

uterus The uterus (from Latin ''uterus'', : uteri or uteruses) or womb () is the hollow organ, organ in the reproductive system of most female mammals, including humans, that accommodates the embryonic development, embryonic and prenatal development, f ...

and

fallopian tubes The fallopian tubes, also known as uterine tubes, oviducts or salpinges (: salpinx), are paired tubular sex organs in the human female body that stretch from the ovaries to the uterus. The fallopian tubes are part of the female reproductive sy ...

. PMDS is primarily caused by a mutation in the

anti-Müllerian hormone Anti-Müllerian hormone (AMH), also known as Müllerian-inhibiting hormone (MIH), is a glycoprotein hormone structurally related to Activin and inhibin, inhibin and activin from the transforming growth factor beta superfamily, whose key roles a ...

(AMH) gene (PMDS Type 1) or AMHR2 gene (PMDS Type 2). In PMDS Type 1, AMH is either not produced, produced in deficient quantities, defective, or secreted at the wrong critical time for male differentiation. PMDS Type 2 is a result of AMH receptor insensitivity to AMH molecules. In a smaller percentage of cases, the cause of PMDS is not fully understood but is related to complex malformations of the urogenital region and paramesonephric ducts during male gonadal development.

References

{{Authority control Developmental biology Embryology of urogenital system Mesoderm