Editing Cellular differentiation (section)

==Mechanisms==
{{See also|Embryonic differentiation waves}}

=== Gene regulatory networks ===
[[Image:Cell Differentiation.jpg|upright=1.5|thumb|Mechanisms of cellular differentiation]]

Each specialized cell type in an organism [[Gene expression|expresses]] a [[subset]] of all the [[gene]]s that constitute the genome of that [[species]]. Each cell type is defined by its particular pattern of [[regulation of gene expression|regulated gene expression]]. Cell differentiation is thus a transition of a cell from one cell type to another and it involves a switch from one pattern of gene expression to another. Cellular differentiation during development can be understood as the result of a [[gene regulatory network]]. A regulatory gene and its cis-regulatory modules are nodes in a gene regulatory network; they receive input and create output elsewhere in the network.<ref name=DeLeon>{{cite journal | vauthors = Ben-Tabou de-Leon S, Davidson EH | title = Gene regulation: gene control network in development | journal = Annual Review of Biophysics and Biomolecular Structure | volume = 36 | issue = 191 | pages = 191–212 | year = 2007 | pmid = 17291181 | doi = 10.1146/annurev.biophys.35.040405.102002 | url = https://resolver.caltech.edu/CaltechAUTHORS:LEOarbbs07 }}</ref> The [[systems biology]] approach to developmental biology emphasizes the importance of investigating how developmental mechanisms interact to produce predictable patterns ([[morphogenesis]]). However, recent research suggests there may be an alternative view. Based on [[stochastic]] gene expression, cellular differentiation is the result of a Darwinian selective process occurring among cells. In this frame, protein and gene networks are the result of cellular processes and not their cause.<ref>{{cite journal | vauthors = Capp JP, Laforge B | title = A Darwinian and Physical Look at Stem Cell Biology Helps Understanding the Role of Stochasticity in Development | language = English | journal = Frontiers in Cell and Developmental Biology | volume = 8 | pages = 659 | date = 23 July 2020 | pmid = 32793600 | pmc = 7391792 | doi = 10.3389/fcell.2020.00659 | doi-access = free }}</ref>

[[File:Signal transduction pathways.svg|thumb|left|240px|An overview of major signal transduction pathways.]]

=== Signaling pathways ===
Cellular differentiation is often controlled by [[cell signaling]]. Many of the signal molecules that convey information from cell to cell during the control of cellular differentiation are called [[growth factor]]s. Although the details of specific [[signal transduction]] pathways vary, these pathways often share the following general steps. A ligand produced by one cell binds to a receptor in the extracellular region of another cell, inducing a conformational change in the receptor. The shape of the cytoplasmic domain of the receptor changes, and the receptor acquires enzymatic activity. The receptor then catalyzes reactions that phosphorylate other proteins, activating them. A cascade of phosphorylation reactions eventually activates a dormant transcription factor or cytoskeletal protein, thus contributing to the differentiation process in the target cell.<ref name=Gilbert>{{cite book | vauthors = Knisely K, Gilbert SF |title=Developmental Biology |publisher=Sinauer Associates |location=Sunderland, Mass |year=2009 |page=147 |isbn=978-0-87893-371-6 |edition=8th }}</ref> Cells and tissues can vary in competence, their ability to respond to external signals.<ref name=Rudel>Rudel and Sommer; The evolution of developmental mechanisms. ''Developmental Biology'' 264, 15-37, 2003 {{cite journal | vauthors = Rudel D, Sommer RJ | title = The evolution of developmental mechanisms | journal = Developmental Biology | volume = 264 | issue = 1 | pages = 15–37 | date = December 2003 | pmid = 14623229 | doi = 10.1016/S0012-1606(03)00353-1 | doi-access = free }}</ref>

=== Inductive signaling ===
Signal induction refers to cascades of signaling events, during which a cell or tissue signals to another cell or tissue to influence its developmental fate.<ref name=Rudel/> Yamamoto and Jeffery<ref name=Yamamoto>Yamamoto Y and WR Jeffery; Central role for the lens in cave fish eye degeneration. '' Science '' 289 (5479), 631-633, 2000 {{cite journal | vauthors = Yamamoto Y, Jeffery WR | title = Central role for the lens in cave fish eye degeneration | journal = Science | volume = 289 | issue = 5479 | pages = 631–633 | date = July 2000 | pmid = 10915628 | doi = 10.1126/science.289.5479.631 | bibcode = 2000Sci...289..631Y }}</ref> investigated the role of the lens in eye formation in cave- and surface-dwelling fish, a striking example of induction.<ref name=Rudel/> Through reciprocal transplants, Yamamoto and Jeffery<ref name=Yamamoto/> found that the lens vesicle of surface fish can induce other parts of the eye to develop in cave- and surface-dwelling fish, while the lens vesicle of the cave-dwelling fish cannot.<ref name=Rudel/>

=== Asymmetric cell division ===
Other important mechanisms fall under the category of [[asymmetric cell division]]s, divisions that give rise to daughter cells with distinct developmental fates. Asymmetric cell divisions can occur because of asymmetrically expressed maternal '''cytoplasmic determinants''' or because of signaling.<ref name="Rudel" /> In the former mechanism, distinct daughter cells are created during [[cytokinesis]] because of an uneven distribution of regulatory molecules in the parent cell; the distinct cytoplasm that each daughter cell inherits results in a distinct pattern of differentiation for each daughter cell. A well-studied example of pattern formation by asymmetric divisions is [[Drosophila embryogenesis#Anterior-posterior axis patterning in Drosophila|body axis patterning in Drosophila]]. [[RNA]] molecules are an important type of intracellular differentiation control signal. The molecular and genetic basis of asymmetric cell divisions has also been studied in green algae of the genus ''[[Volvox]]'', a model system for studying how unicellular organisms can evolve into multicellular organisms.<ref name="Rudel" /> In ''Volvox carteri'', the 16 cells in the anterior hemisphere of a 32-cell embryo divide asymmetrically, each producing one large and one small daughter cell. The size of the cell at the end of all cell divisions determines whether it becomes a specialized germ or somatic cell.<ref name="Rudel" /><ref name="Kirk">Kirk MM, A Ransick, SE Mcrae, DL Kirk; The relationship between cell size and cell fate in ''Volvox carteri''. ''Journal of Cell Biology'' 123, 191-208, 1993 {{cite journal | vauthors = Kirk MM, Ransick A, McRae SE, Kirk DL | title = The relationship between cell size and cell fate in Volvox carteri | journal = The Journal of Cell Biology | volume = 123 | issue = 1 | pages = 191–208 | date = October 1993 | pmid = 8408198 | pmc = 2119814 | doi = 10.1083/jcb.123.1.191 }}</ref>

=== Evolutionary perspectives on mechanisms ===
While [[evolution]]arily conserved molecular processes are involved in the cellular mechanisms underlying these switches, in animal species these are very different from the well-characterized [[operon|gene regulatory mechanisms]] of [[bacteria]], and even from those of the animals' closest [[holozoa|unicellular relatives]].<ref name="Newman">{{cite journal | vauthors = Newman SA | title = Cell differentiation: What have we learned in 50 years? | journal = Journal of Theoretical Biology | volume = 485 | pages = 110031 | date = January 2020 | pmid = 31568790 | doi = 10.1016/j.jtbi.2019.110031 | bibcode = 2020JThBi.48510031N | arxiv = 1907.09551 | doi-access = free }}</ref> Specifically, cell differentiation in animals is highly dependent on [[biomolecular condensate]]s of regulatory proteins and [[Enhancer (genetics)|enhancer]] DNA sequences.