Cell fate determination
Within the field of
Cell fate
The development of new molecular tools including
During embryogenesis, for a number of cell cleavages (the specific number depends on the type of organism) all the cells of an embryo will be morphologically and developmentally equivalent. This means, each cell has the same development potential and all cells are essentially interchangeable, thus establishing an equivalence group. The developmental equivalence of these cells is usually established via transplantation and cell ablation experiments. As embryos mature, more complex fate determination occurs as structures appear, and cells differentiate, beginning to perform specific functions. Under normal conditions, once cells have a specified fate and have undergone cellular differentiation, they generally cannot return to less specified states; however, new research indicates that de-differentiation is possible under certain conditions including wound healing and cancer.[16][17]
The determination of a cell to a particular fate can be broken down into two states where the cell can be specified (committed) or determined. In the state of being committed or specified, the cell type is not yet determined and any bias the cell has toward a certain fate can be reversed or transformed to another fate. If a cell is in a determined state, the cell's fate cannot be reversed or transformed. In general, this means that a cell determined to differentiate into a brain cell cannot be transformed into a skin cell. Determination is followed by differentiation, the actual changes in biochemistry, structure, and function that result in specific cell types. Differentiation often involves a change in appearance as well as function.[18]
Modes of specification
There are three general ways a cell can become specified for a particular fate; they are autonomous specification, conditional specification and syncytial specification.[19]
Autonomous specification
This type of specification results from cell-intrinsic properties; it gives rise to mosaic development. The cell-intrinsic properties arise from a cleavage of a cell with asymmetrically expressed maternal cytoplasmic determinants (proteins, small regulatory RNAs and mRNA). Thus, the fate of the cell depends on factors secreted into its cytoplasm during cleavage. Autonomous specification was demonstrated in 1887 by a French medical student, Laurent Chabry, working on tunicate embryos.[20][21] This asymmetric cell division usually occurs early in embryogenesis.
Positive feedback can create asymmetry from homogeneity. In cases where the external or stimuli that would cause asymmetry are very weak or disorganized, through positive feedback the system can spontaneously pattern itself. Once the feedback has begun, any small initial signaling is magnified and thus produces an effective patterning mechanism.
The specific results of cell ablation and isolation that highlights autonomously specified cells are the following. If ablation of a tissue from a certain cell occurred, the cell will have a missing part. As a result, the removed tissue was autonomously specified since the cell was not able to make up for the missing part [19][20][23]. Furthermore, if specific cells were isolated in a petri dish from the whole structure, these cells will still form the structure or tissue they were going to form initially.[19][20][23] In other words, the signaling to form a specific tissue is within the tissue not coming from a central organ or system.
Conditional specification
In contrast to the autonomous specification, this type of specification is a cell-extrinsic process that relies on cues and interactions between cells or from concentration-gradients of morphogens. Inductive interactions between neighboring cells is the most common mode of tissue patterning. In this mechanism, one or two cells from a group of cells with the same developmental potential are exposed to a signal (morphogen) from outside the group. Only the cells exposed to the signal are induced to follow a different developmental pathway, leaving the rest of the equivalence group unchanged. Another mechanism that determines the cell fate is regional determination (see
In conditionally specified cells, the designated cell requires signaling from an exterior cell. Therefore, if the tissue was ablated, the cell will be able to regenerate or signal to reform the initially ablated tissue.[19][20][23] In addition, if a belly tissue for example was removed and transplanted in the back, the new forming tissue will be a back tissue.[19][20][23] This result is seen because the surrounding cells and tissues influence the newly forming cell.
Syncytial specification
This type of a specification is a hybrid of the autonomous and conditional that occurs in insects. This method involves the action of morphogen gradients within the syncytium. As there are no cell boundaries in the syncytium, these morphogens can influence nuclei in a concentration-dependent manner. It was discovered that cellularization of the blastoderm took place either during or before the specifications of body regions.[26] Also, one cell could contain more than one nucleus due to fusion of multiple uninuclear cells. As a result, the variable cleavage of the cells will make the cells hard to be committed or determined to one cell fate.[23] At the end of cellularization, the autonomously specified cells become distinguished from the conditionally specified once.
See also
For a good review of the part of the history of morphogen signaling and development see Briscoe J, Making a grade: Sonic Hedgehog signalling and the control of neural cell fate.[28]
In systems biology, cell-fate determination is predicted to exhibit certain dynamics, such as attractor-convergence (the attractor can be an equilibrium point, limit cycle or
References
- PMID 12062082.
- PMID 25710534.
- PMID 11061565.
- PMID 18192179.
- PMID 19118209.
- ISBN 978-0-444-51924-5, retrieved 2021-03-22
- S2CID 14633229.
- PMID 15271302.
- PMID 10221902.
- S2CID 27988180.
- PMID 19253398.
- PMID 19447051.
- PMID 18539629.
- ^ "Multiplex mode for the LSM 9 series with Airyscan 2: fast and gentle confocal super-resolution in large volumes" (PDF).
- PMID 25657347.
- PMID 24531722.
- PMID 29938761.
- S2CID 235336596.
- ^ ISBN 978-0-87893-250-4.
- ^ a b c d e Gilbert, S. F. (2000). Developmental Biology (6th ed.).
- PMID 4198663.
- ^ S2CID 4396489.
- ^ a b c d e Gilbert, Scott (2014). Developmental Biology (10 ed.). Sinauer Associates, Inc.
- PMID 20412781.
- PMID 5833110.
- S2CID 11443065.
- PMID 20031252.
- PMID 19197245.
- S2CID 2579314.