Schematic of Cell State Splitter Organelle

How_Embryonic_Differentiation_Waves_Create_Gradients

Signal Transduction Model for Embryonic Differentiation Waves

A mechanochemical based model for primary neural induction was first proposed in 1985 by Brodland and Gordon. They proposed that there is a mechanically sensitive bistable

organelle In cell biology, an organelle is a specialized subunit, usually within a cell (biology), cell, that has a specific function. The name ''organelle'' comes from the idea that these structures are parts of cells, as Organ (anatomy), organs are to th ...

made of

microtubules 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 ...

and

microfilaments Microfilaments, also called actin filaments, are protein filaments in the cytoplasm of eukaryotic cells that form part of the cytoskeleton. They are primarily composed of polymers of actin, but are modified by and interact with numerous other p ...

in the apical ends of cells within cell sheets that are about to differentiate (that are competent) and these cells are under mechanical tension. The microtubules and microfilaments are in mechanical opposition in a proposed embryonic organelle they called the cell state splitter. Depending on where the cell is within a sheet, the tension will be resolved by either the apical end contracting or the apical end expanding. The resolution will begin at one point and spread over the rest of the tissue limited by other mechanical forces at boundaries. An actual physical wave of contraction has been found which traverses the presumptive neural

epithelium 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 ...

of the developing salamander, the

axolotl The axolotl (; from ) (''Ambystoma mexicanum'') is a neoteny, paedomorphic salamander, one that Sexual maturity, matures without undergoing metamorphosis into the terrestrial adult form; adults remain Aquatic animal, fully aquatic with obvio ...

(''Ambystoma mexicanum''). The contraction wave's trajectory was more complex than predicted in the original model however it did originate from the precise location of the Spemann organizer and traversed only the presumptive neural epithelium. Electron microscopy showed

intermediate filaments Intermediate filaments (IFs) are cytoskeletal structural components found in the cells of vertebrates, and many invertebrates. Homologues of the IF protein have been noted in an invertebrate, the cephalochordate ''Branchiostoma''. Intermedi ...

are also present in the cell state splitter. Additional waves of both contraction and expansion were also discovered by time lapse photography of axolotl

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 ...

. Among them was a wave of expansion that occurs in ectoderm only in the presumptive epithelium. When the trajectories of the waves were superimposed on the

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

of the axolotl it was shown that there is a unique combination of expansion and contraction waves that correlates with the tissue types determined during gastrulation and that this set of wave trajectories could explain the shape of the fate map. A biochemical basis for the

signal transduction Signal transduction is the process by which a chemical or physical signal is transmitted through a cell as a biochemical cascade, series of molecular events. Proteins responsible for detecting stimuli are generally termed receptor (biology), rece ...

from the cytoskeleton to the nucleus resulting in changes in gene expression was first proposed by Björklund (now Gordon) and Gordon in 1993 This would result in a biochemical transduction of the biomechanical signal from the

cytoskeleton The cytoskeleton is a complex, dynamic network of interlinking protein filaments present in the cytoplasm of all cells, including those of bacteria and archaea. In eukaryotes, it extends from the cell nucleus to the cell membrane and is compos ...

that is thereby passed on to the nucleus. This then signals the changes in gene expression. If the cell has experienced contraction, one signal is sent and if the cell has experienced expansion then another signal is sent. The signal from the cytoskeleton is what causes determination of cell fate. The phenomena of gene gradients during development is dismissed as an epiphenomena resulting from the passage of the biomechanical wave initiating changes in gene expression in individual cells as the wave passes through a cell sheet. They have outlined their research and their theory of differentiation waves in detail in their book ''Embryogenesis Explained''. For example, the first differentiation that takes place during mammalian compaction is explained in terms of their differentiation waves model thus; Cells on the outside of the

morula In embryology, cleavage is the division of cells in the early development of the embryo, following fertilization. The zygotes of many species undergo rapid cell cycles with no significant overall growth, producing a cluster of cells the same siz ...

expand due to the effect of their position on the outside of the early ball of cells and they become determined to be

trophoblast The trophoblast (from Greek language, Greek : to feed; and : germinator) is the outer layer of cells of the blastocyst. Trophoblasts are present four days after Human fertilization, fertilization in humans. They provide nutrients to the embryo an ...

. Cells on the inside of the ball contract instead due to the mechanical force of being on the inside and they become determined to be the

inner cell mass The inner cell mass (ICM) or embryoblast (known as the pluriblast in marsupials) is a structure in the early development of an embryo. It is the mass of cells inside the blastocyst that will eventually give rise to the definitive structures of t ...

. All the other activity, such as changes in gene expression, signalling proteins, release of

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, and epigenetic changes, are considered the result of differentiation after the response of the cytoskeleton to mechanical signals which then determines cell fate using purely mechanical signals. Failure of

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 folds become elevated, ...

closure is explained as a failure of methylation of cytoskeleton of developing neural tissue for those

neural tube defects Neural tube defects (NTDs) are a group of birth defects in which an opening in the spine or cranium remains from early in human development. In the third week of pregnancy called gastrulation, specialized cells on the dorsal side of the embry ...

which are

folate Folate, also known as vitamin B9 and folacin, is one of the B vitamins. Manufactured folic acid, which is converted into folate by the body, is used as a dietary supplement and in food fortification as it is more stable during processing and ...

sensitive and prevented by

folic acid Folate, also known as vitamin B9 and folacin, is one of the B vitamins. Manufactured folic acid, which is converted into folate by the body, is used as a dietary supplement and in food fortification as it is more stable during processing and ...

supplementation.Björklund NK, Gordon
A hypothesis linking low folate intake to neural tube defects due to failure of post-translation methylations of the cytoskeleton
Int. J. Dev. Biol. 50: 135 - 141 2006

References

*{{CCBYSASource, sourcepath=https://biology.stackexchange.com/questions/9276/which-exact-mechanism-triggers-the-first-cell-differentiation-after-n-divisions, sourcearticle=which exact mechanism triggers the first cell differentiation after n divisions?, authors(s)=Angela Olsen Embryology