Morphogenesis
Encyclopedia
Morphogenesis is the biological process
that causes an organism
to develop its shape. It is one of three fundamental aspects of developmental biology
along with the control of cell growth
and cellular differentiation
.
The process controls the organized spatial distribution of cells during the embryonic development
of an organism
. Morphogenesis can take place also in a mature organism, in cell culture
or inside tumor cell masses. Morphogenesis also describes the development of unicellular life forms that do not have an embryonic stage in their life cycle, or describes the evolution
of a body structure within a taxonomic group
.
Morphogenetic responses may be induced in organisms by hormone
s, by environmental chemicals ranging from substances produced by other organisms to toxic chemicals
or radionuclides released as pollutants, and other plants, or by mechanical stresses induced by spatial patterning of the cells.
and Alan Turing
. These works postulated the presence of chemical signals and physico-chemical processes such as diffusion, activation, and deactivation in cellular and organismic growth. The fuller understanding of the mechanisms involved in actual organisms required the discovery of DNA
and the development of molecular biology
and biochemistry
.
The term Histomorphogenesis was coined by Ricqlès et al. (2001) for the same process in the bone histology.
s are soluble molecules that can diffuse and carry signals that control cell differentiation decisions in a concentration-dependent fashion. Morphogens typically act through binding to specific protein receptor
s. An important class of molecules involved in morphogenesis are transcription factor
proteins that determine the fate of cells by interacting with DNA
. These can be coded for by master regulatory gene
s and either activate or deactivate the transcription
of other genes; in turn, these secondary gene products can regulate the expression of still other genes in a regulatory cascade. Another class of molecules involved in morphogenesis are molecules that control cell adhesion
. For example, during gastrulation
, clumps of stem cell
s switch off their cell-to-cell adhesion, become migratory, and take up new positions within an embryo where they again activate specific cell adhesion proteins and form new tissues and organs. Several examples that illustrate the roles of morphogens, transcription factor
s and cell adhesion molecules in morphogenesis are discussed below.
Morphogenesis arises because of changes in the cellular structure or how cells interact in tissues. Certain cell types "sort out". Cell "sorting out" means that when the cells physically interact they move so as to sort into clusters that maximize contact between cells of the same type. The ability of cells to do this comes from differential cell adhesion. Two well-studied types of cells that sort out are epithelial cells and mesenchymal cells
. During embryonic development there are some cellular differentiation
events during which mesenchymal cells become epithelial cells and at other times epithelial cells differentiate into mesenchymal cells (see Epithelial-mesenchymal transition
). Following epithelial-mesenchymal transition, cells can migrate away from an epithelium and then associate with other similar cells in a new location.
cells that have the strongest adhesion move to the center of a mixed aggregates of cells.
The molecules responsible for adhesion are called cell adhesion molecules (CAMs). Several types of cell adhesion molecules are known and one major class of these molecules are cadherins. There are dozens of different cadherins that are expressed on different cell types. Cadherins bind to other cadherins in a like-to-like manner: E-cadherin (found on many epithelial cells) binds preferentially to other E-cadherin molecules. Mesenchymal cells usually express other cadherin types such as N-cadherin.
(ECM) is involved with separating tissues, providing structural support or providing a structure for cells to migrate on. Collagen
, laminin
, and fibronectin
are major ECM molecules that are secreted and assembled into sheets, fibers, and gels. Multisubunit transmembrane receptors called integrin
s are used to bind to the ECM. Integrins bind extracellularly to fibronectin, laminin, or other ECM components, and intracellularly to microfilament
-binding proteins α-actinin
and talin to link the cytoskeleton
with the outside. Integrins also serve as receptors to trigger signal transduction
cascades when binding to the ECM. A well-studied example of morphogenesis that involves ECM is mammary gland
ductal branching.
Biological process
A biological process is a process of a living organism. Biological processes are made up of any number of chemical reactions or other events that results in a transformation....
that causes an organism
Organism
In biology, an organism is any contiguous living system . In at least some form, all organisms are capable of response to stimuli, reproduction, growth and development, and maintenance of homoeostasis as a stable whole.An organism may either be unicellular or, as in the case of humans, comprise...
to develop its shape. It is one of three fundamental aspects of developmental biology
Developmental biology
Developmental biology is the study of the process by which organisms grow and develop. Modern developmental biology studies the genetic control of cell growth, differentiation and "morphogenesis", which is the process that gives rise to tissues, organs and anatomy.- Related fields of study...
along with the control of cell growth
Cell growth
The term cell growth is used in the contexts of cell development and cell division . When used in the context of cell division, it refers to growth of cell populations, where one cell grows and divides to produce two "daughter cells"...
and cellular differentiation
Cellular differentiation
In developmental biology, cellular differentiation is the process by which a less specialized cell becomes a more specialized cell type. Differentiation occurs numerous times during the development of a multicellular organism as the organism changes from a simple zygote to a complex system of...
.
The process controls the organized spatial distribution of cells during the embryonic development
Developmental biology
Developmental biology is the study of the process by which organisms grow and develop. Modern developmental biology studies the genetic control of cell growth, differentiation and "morphogenesis", which is the process that gives rise to tissues, organs and anatomy.- Related fields of study...
of an organism
Organism
In biology, an organism is any contiguous living system . In at least some form, all organisms are capable of response to stimuli, reproduction, growth and development, and maintenance of homoeostasis as a stable whole.An organism may either be unicellular or, as in the case of humans, comprise...
. Morphogenesis can take place also in a mature organism, in cell culture
Cell culture
Cell culture is the complex process by which cells are grown under controlled conditions. In practice, the term "cell culture" has come to refer to the culturing of cells derived from singlecellular eukaryotes, especially animal cells. However, there are also cultures of plants, fungi and microbes,...
or inside tumor cell masses. Morphogenesis also describes the development of unicellular life forms that do not have an embryonic stage in their life cycle, or describes the evolution
Evolution
Evolution is any change across successive generations in the heritable characteristics of biological populations. Evolutionary processes give rise to diversity at every level of biological organisation, including species, individual organisms and molecules such as DNA and proteins.Life on Earth...
of a body structure within a taxonomic group
Taxonomy
Taxonomy is the science of identifying and naming species, and arranging them into a classification. The field of taxonomy, sometimes referred to as "biological taxonomy", revolves around the description and use of taxonomic units, known as taxa...
.
Morphogenetic responses may be induced in organisms by hormone
Hormone
A hormone is a chemical released by a cell or a gland in one part of the body that sends out messages that affect cells in other parts of the organism. Only a small amount of hormone is required to alter cell metabolism. In essence, it is a chemical messenger that transports a signal from one...
s, by environmental chemicals ranging from substances produced by other organisms to toxic chemicals
Toxin
A toxin is a poisonous substance produced within living cells or organisms; man-made substances created by artificial processes are thus excluded...
or radionuclides released as pollutants, and other plants, or by mechanical stresses induced by spatial patterning of the cells.
History
Some of the earliest ideas on how physical and mathematical processes and constraints affect biological growth were written by D'Arcy Wentworth ThompsonD'Arcy Wentworth Thompson
Sir D'Arcy Wentworth Thompson CB FRS FRSE was a Scottish biologist, mathematician, and classics scholar. A pioneering mathematical biologist, he is mainly remembered as the author of the 1917 book On Growth and Form, written largely in Dundee in 1915...
and Alan Turing
Alan Turing
Alan Mathison Turing, OBE, FRS , was an English mathematician, logician, cryptanalyst, and computer scientist. He was highly influential in the development of computer science, providing a formalisation of the concepts of "algorithm" and "computation" with the Turing machine, which played a...
. These works postulated the presence of chemical signals and physico-chemical processes such as diffusion, activation, and deactivation in cellular and organismic growth. The fuller understanding of the mechanisms involved in actual organisms required the discovery of DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
and the development of molecular biology
Molecular biology
Molecular biology is the branch of biology that deals with the molecular basis of biological activity. This field overlaps with other areas of biology and chemistry, particularly genetics and biochemistry...
and biochemistry
Biochemistry
Biochemistry, sometimes called biological chemistry, is the study of chemical processes in living organisms, including, but not limited to, living matter. Biochemistry governs all living organisms and living processes...
.
The term Histomorphogenesis was coined by Ricqlès et al. (2001) for the same process in the bone histology.
Molecular basis
Several types of molecules are particularly important during morphogenesis. MorphogenMorphogen
A morphogen is a substance governing the pattern of tissue development, and the positions of the various specialized cell types within a tissue...
s are soluble molecules that can diffuse and carry signals that control cell differentiation decisions in a concentration-dependent fashion. Morphogens typically act through binding to specific protein receptor
Receptor (biochemistry)
In biochemistry, a receptor is a molecule found on the surface of a cell, which receives specific chemical signals from neighbouring cells or the wider environment within an organism...
s. An important class of molecules involved in morphogenesis are transcription factor
Transcription factor
In molecular biology and genetics, a transcription factor is a protein that binds to specific DNA sequences, thereby controlling the flow of genetic information from DNA to mRNA...
proteins that determine the fate of cells by interacting with DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
. These can be coded for by master regulatory gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
s and either activate or deactivate the transcription
Transcription (genetics)
Transcription is the process of creating a complementary RNA copy of a sequence of DNA. Both RNA and DNA are nucleic acids, which use base pairs of nucleotides as a complementary language that can be converted back and forth from DNA to RNA by the action of the correct enzymes...
of other genes; in turn, these secondary gene products can regulate the expression of still other genes in a regulatory cascade. Another class of molecules involved in morphogenesis are molecules that control cell adhesion
Cell adhesion
Cellular adhesion is the binding of a cell to a surface, extracellular matrix or another cell using cell adhesion molecules such as selectins, integrins, and cadherins. Correct cellular adhesion is essential in maintaining multicellular structure...
. For example, during gastrulation
Gastrulation
Gastrulation is a phase early in the embryonic development of most animals, during which the single-layered blastula is reorganized into a trilaminar structure known as the gastrula. These three germ layers are known as the ectoderm, mesoderm, and endoderm.Gastrulation takes place after cleavage...
, clumps of stem cell
Stem cell
This article is about the cell type. For the medical therapy, see Stem Cell TreatmentsStem cells are biological cells found in all multicellular organisms, that can divide and differentiate into diverse specialized cell types and can self-renew to produce more stem cells...
s switch off their cell-to-cell adhesion, become migratory, and take up new positions within an embryo where they again activate specific cell adhesion proteins and form new tissues and organs. Several examples that illustrate the roles of morphogens, transcription factor
Transcription factor
In molecular biology and genetics, a transcription factor is a protein that binds to specific DNA sequences, thereby controlling the flow of genetic information from DNA to mRNA...
s and cell adhesion molecules in morphogenesis are discussed below.
Cellular basis
Mesenchyme
Mesenchyme, or mesenchymal connective tissue, is a type of undifferentiated loose connective tissue that is derived mostly from mesoderm, although some are derived from other germ layers; e.g. some mesenchyme is derived from neural crest cells and thus originates from the ectoderm...
. During embryonic development there are some cellular differentiation
Cellular differentiation
In developmental biology, cellular differentiation is the process by which a less specialized cell becomes a more specialized cell type. Differentiation occurs numerous times during the development of a multicellular organism as the organism changes from a simple zygote to a complex system of...
events during which mesenchymal cells become epithelial cells and at other times epithelial cells differentiate into mesenchymal cells (see Epithelial-mesenchymal transition
Epithelial-mesenchymal transition
Epithelial-mesenchymal transition or transformation is a hypothesized program of development of biological cells characterized by loss of cell adhesion, repression of E-cadherin expression, and increased cell mobility...
). Following epithelial-mesenchymal transition, cells can migrate away from an epithelium and then associate with other similar cells in a new location.
Adhesion
During embryonic development, cells are restricted to different layers due to differential affinities. One of the ways this can occur is when cells share the same cell-to-cell adhesion molecules. For instance, homotypic cell adhesion can maintain boundaries between groups of cells that have different adhesion molecules. Furthermore, cells can sort based upon differences in adhesion between the cells, so even two populations of cells with different levels of the same adhesion molecule can sort out. In cell cultureCell culture
Cell culture is the complex process by which cells are grown under controlled conditions. In practice, the term "cell culture" has come to refer to the culturing of cells derived from singlecellular eukaryotes, especially animal cells. However, there are also cultures of plants, fungi and microbes,...
cells that have the strongest adhesion move to the center of a mixed aggregates of cells.
The molecules responsible for adhesion are called cell adhesion molecules (CAMs). Several types of cell adhesion molecules are known and one major class of these molecules are cadherins. There are dozens of different cadherins that are expressed on different cell types. Cadherins bind to other cadherins in a like-to-like manner: E-cadherin (found on many epithelial cells) binds preferentially to other E-cadherin molecules. Mesenchymal cells usually express other cadherin types such as N-cadherin.
Extracellular matrix
The extracellular matrixExtracellular matrix
In biology, the extracellular matrix is the extracellular part of animal tissue that usually provides structural support to the animal cells in addition to performing various other important functions. The extracellular matrix is the defining feature of connective tissue in animals.Extracellular...
(ECM) is involved with separating tissues, providing structural support or providing a structure for cells to migrate on. Collagen
Collagen
Collagen is a group of naturally occurring proteins found in animals, especially in the flesh and connective tissues of mammals. It is the main component of connective tissue, and is the most abundant protein in mammals, making up about 25% to 35% of the whole-body protein content...
, laminin
Laminin
Laminins are major proteins in the basal lamina , a protein network foundation for most cells and organs...
, and fibronectin
Fibronectin
Fibronectin is a high-molecular weight glycoprotein of the extracellular matrix that binds to membrane-spanning receptor proteins called integrins. In addition to integrins, fibronectin also binds extracellular matrix components such as collagen, fibrin and heparan sulfate proteoglycans...
are major ECM molecules that are secreted and assembled into sheets, fibers, and gels. Multisubunit transmembrane receptors called integrin
Integrin
Integrins are receptors that mediate attachment between a cell and the tissues surrounding it, which may be other cells or the ECM. They also play a role in cell signaling and thereby regulate cellular shape, motility, and the cell cycle....
s are used to bind to the ECM. Integrins bind extracellularly to fibronectin, laminin, or other ECM components, and intracellularly to microfilament
Microfilament
Microfilaments are the thinnest filaments of the cytoskeleton, a structure found in the cytoplasm of all eukaryotic cells. These linear polymers of actin subunits are flexible and relatively strong, resisting buckling by multi-piconewton compressive forces and filament fracture by nanonewton...
-binding proteins α-actinin
ACTN1
Alpha-actinin-1 is a protein that in humans is encoded by the ACTN1 gene.-Interactions:Actinin, alpha 1 has been shown to interact with PDLIM1, Collagen, type XVII, alpha 1, CDK5R1, Zyxin, Protein kinase N1, GIPC1, SSX2IP and CDK5R2....
and talin to link the cytoskeleton
Cytoskeleton
The cytoskeleton is a cellular "scaffolding" or "skeleton" contained within a cell's cytoplasm and is made out of protein. The cytoskeleton is present in all cells; it was once thought to be unique to eukaryotes, but recent research has identified the prokaryotic cytoskeleton...
with the outside. Integrins also serve as receptors to trigger signal transduction
Signal transduction
Signal transduction occurs when an extracellular signaling molecule activates a cell surface receptor. In turn, this receptor alters intracellular molecules creating a response...
cascades when binding to the ECM. A well-studied example of morphogenesis that involves ECM is mammary gland
Mammary gland
A mammary gland is an organ in mammals that produces milk to feed young offspring. Mammals get their name from the word "mammary". In ruminants such as cows, goats, and deer, the mammary glands are contained in their udders...
ductal branching.
See also
- EmbryogenesisEmbryogenesisEmbryogenesis is the process by which the embryo is formed and develops, until it develops into a fetus.Embryogenesis starts with the fertilization of the ovum by sperm. The fertilized ovum is referred to as a zygote...
- Pattern formationPattern formationThe science of pattern formation deals with the visible, orderly outcomes of self-organisation and the common principles behind similar patterns....
- French flag modelFrench flag modelThe French Flag Model is a conceptual definition of a morphogen, described by Lewis Wolpert in the 1960s. A morphogen is rigorously defined as a signaling molecule that acts directly on cells to produce specific cellular responses dependent on morphogen concentration...
- Reaction-diffusion
- NeurulationNeurulationNeurulation is the stage of organogenesis in vertebrate embryos, during which the neural tube is transformed into the primitive structures that will later develop into the central nervous system....
- GastrulationGastrulationGastrulation is a phase early in the embryonic development of most animals, during which the single-layered blastula is reorganized into a trilaminar structure known as the gastrula. These three germ layers are known as the ectoderm, mesoderm, and endoderm.Gastrulation takes place after cleavage...
- Axon guidanceAxon guidanceAxon guidance is a subfield of neural development concerning the process by which neurons send out axons to reach the correct targets...
- Eye developmentEye developmentThe eye develops from the neural tube, the epidermis, and the periocular mesenchyme, which receives contributions from both the neural crest and mesoderm lineages.-Sequential inductions:...
- Polycystic kidney disease 2Polycystic kidney disease 2Polycystin-2 is a protein that in humans is encoded by the PKD2 gene.-Interactions:Polycystic kidney disease 2 has been shown to interact with TRPC1, PKD1 and TNNI3.-External links:* -Further reading:...
- Drosophila embryogenesisDrosophila embryogenesisDrosophila embryogenesis, the process by which Drosophila embryos form, is a favorite model system for geneticists and developmental biologists studying embryogenesis. The small size, short generation time, and large brood size make it ideal for genetic studies. Transparent embryos facilitate...