Key-Notes: basic concepts in Developmental Biology
| Site: | Cell Molecular Biology |
| Course: | Developmental Neurobiology 2017-2018 |
| Book: | Key-Notes: basic concepts in Developmental Biology |
| Printed by: | Guest user |
| Date: | Friday, 22 November 2024, 1:56 AM |
Description
Key-Notes
1. Introduction
These Key-Notes aim to provide the students with a summary of some basic concepts of developmental biology that are fundamental to approach the study of nervous system development.
Development is a gradual process by which a complex multicellular organism arises from a single cell (the zygote). It involves 5 major overlapping processes:
- growth = increase in size
- cell division= increase in number
- differentiation = diversification of cell types
- pattern formation = organization
- morphogenesis = generation of shapes and structures
For a general overview on the stages of animal development refer to the online version of the book "Developmental biology, 6th edition - Chapter 2 - The Circle of Life: The Stages of Animal Development
2. Differentiation
Cell differentiation is the process by which cells become structurally and functionally specialized, allowing the formation of distinct cell types (e.g in the nervous system: different types of neurons and glial cells).
The structural and functional specificity of a cell depends on the proteins it synthesizes. Recently, emerging evidence has shown the importance of noncoding RNA regulation in multiple developmental processes, including cell differentiation.
With very few exceptions, all cells of a given organism contain the same genetic information (genomic equivalence). Differentiated cells are genetically identical but express different genes. Thus the process of differentiation involves the control and maintenance of differential gene expression.
3. Fate and commitment
The number of different cell types in the embryo increases as development proceeds.
Cell fate describes the range of cell types a particular cell can give rise to during normal development.
Cell potency describes the entire repertoire of cell types a particular cell can give rise in all possible environments (e.g. a cell can differentiate in an abnormal way if it is experimentally grafted in an ectopic region). The potency of a cell is an intrinsic property and is greater than or equal to its fate.
The fate of a cell depends on its potency + its environment (e.g. its contact with other cells in the embryo).
In animal development, cell fate and potency are progressively restricted (from totipotent to unipotent) until a cell become terminally differentiated (can only form a single cell type). NB. stem cells are an exception because they are never terminally differentiated.
As cell fate becomes restricted following each decision in the developmental hierarchy, cells are said to be committed to a certain fate. In animals commitment occurs in stages.
4. Mechanisms of developmental commitment
Two main strategies are used for establishing commitment and thus initiating the series of events that result in cell differentiation: inheritance of cytoplasmic determinants and perception of external inductive signals.
Cytoplasmic determinants
A cell can divide to produce 2 daughter cells committed to different fates. This can be achieved through the asymmetric distribution of cytoplasmic factors (e.g. proteins and RNAs) that can influence the fate of the daughter cells. Cytoplasmic determinants are found in many developmental systems: this strategy is used frequently in early development, when maternal gene products, localized to particular egg regions, are asymmetrically distributed to different blastomeres during cleavage.
Fig. 3 Intrinsic asymmetry localizes polarity proteins (red), which instruct cell fate determinants (green) to segregate asymmetrically during mitosis in the absence of extracellular cues (DNA, blue)-Modified from Neumuller & Knoblich GENES & DEVELOPMENT 23:2675–2699, 2009
Inductive signals
Unlike the segregation of cytoplasmic determinants, induction is an extrinsic process that depends on the position of a cell in the embryo. Induction is a process whereby one cell or group of cells can influence the developmental fate of another, and is a common strategy to control differentiation and pattern formation in development. Two identical cells can follow different fates if one is exposed to an external signal (often produced by a different cell) while the other is not.
The inductive signal can be a protein or another molecule (secreted by the inducing cell) that interacts with a receptor on the surface of the responding cell (although some inductive signals pass the cell membrane and interact with cytosolic receptors). The signal initiates a signal transduction cascade that influence the activity of transcription factors and/or other proteins eventually altering the pattern of gene expression. Responding cells may show a single stereotyped response to the inductive signal, or a graded response dependent on its concentration, in which case it is called a morphogen*.
The response to inductive signals depends on the ability of the cell to receive the signal and react in an appropriate manner. This ability is called competence. The loss of competence (e.g. loss of cell surface receptors, signal transduction apparatus, or downstream target transcription factors) is one mechanism by which cells become irreversibly committed to a given developmental pathway. In other words the cell is no longer able to respond to the inductive signals.
Two types of induction can be distinguished on the basis of the choices available to the responding cell: instructive and permissive induction. Instructive induction occurs where the responding cell has a choice of fates and will follow one developmental pathway following induction, and an alternative pathway in absence of the inductive signals. In example, in the early Xenopus embryo, ectoderm will form the neural plate in presence of inductive signals from the notochord, but epidermis in the absence of induction. Permissive induction occurs where the responding cell is already committed to a certain fate, and requires the inducing signal to proceed in the developmental pathway.
Read more on cell-cell communication and inductive signals at http://www.ncbi.nlm.nih.gov/books/NBK9999/
5. lateral inhibition
It is a special form of induction occurring during development, involving an initially equivalent field of cells and resulting in the differentiation of individual cells in a regularly spaced pattern.
Lateral inhibition is involved in different developmental processes including the control of the choice of neuronal progenitors in Drosophila and vertebrates.
Fig.4 from Molecular Biology of the Cell. 3rd edition. Alberts B, Bray D, Lewis J, et al.
New York: Garland Science; 1994.
The figure on the left shows a group of cells in the undifferentiated state - they all have the potential to differentiate in the same way, and they all signal to each other to repress differentiation.
The figure in the center shows that as individual cells (in blue) begin to produce more inhibitor signal through random fluctuation begin to differentiate and suppress the differentiation of surrounding cells. This can be achieved not only by increasing the production of the inhibitory signal but also by decreasing the synthesis of its receptor. The spacing of the differentiated cells would be regulated by the range of the signal and the strength of its effect.
6. Mosaic and Regulative development
Mosaic vs Regulative development
As we have seen from the previous paragraph cytoplasmic determinants and inductive signals can both be used to control cell fate during development.
If development was exclusively controlled by cytoplasmic determinants, the fate of every cell would depend uniquely on its lineage, while its position in the embryo would be irrelevant. This is the definition of mosaic development.
On the other hand, if development was controlled exclusively by inductive signals, the fate of every cell would depend mostly on its position in the embryo. This is the definition of regulative development.
The development of most organisms involves a combination of both mechanisms.
In mosaic development: Cell Fate = Cell Potency
The fate of the cell is governed entirely by its intrinsic characteristics, i.e. cytoplasmic determinants it inherits at cell division. During development each cell is said to undergo autonomous specification. If the cell is removed from the embryo it should, in principle, develop according to its intrinsic instructions and differentiate into the appropriate part of the embryo even if the rest of the embryo is not there.
In regulative development :Cell Potency is greater than Cell Fate
The fate of the cell is governed by its interactions with other cells. Each cell is said to undergo conditional specification. If the cell is removed from the embryo it should not fulfill its normal fate because it lacks the necessary interactions.
Read more informations on mosaic and regulative development on the book chapter "The developmental mechanics of cell specification"
7. Pattern formation
Pattern formation
All embryos of a given species have a similar structure or body plan.
How does it occur?
During development each cell must differentiate according to its position in the embryo, so that the "correct" cell types arise in the correct place. In other words, cells must know where they are in relation to other cells in the embryo. This is achieved by giving each cells a positional value in relation to the principle embryonic axes.
Regional specification describes any mechanism that tells a cell where it is in relation to other cells in the embryo, so that it can behave in a manner appropriate for its position. Regional specification is essential for pattern formation.
Keys question in developmental biology are:
How cells become aware of their position? What is the nature of the positional information they receive?
Several model systems indicate that cells may acquire positional values on the basis of their distance from a source of a morphogen.
Morphogens
A Morphogen is a secreted substance that can influence cell fate (.i.e. specify multiple cell fates) having different effects at different concentrations. In its simplest model, the positional information along an axis can be generated by the synthesis of a morphogen at a source at one end of the axis, and diffusion away from the source would set up a morphogen gradient.
Cells at different position along the axis would receive different concentrations of the morphogen and this would induce different patterns of gene expression at different concentration thresholds. Such concentration-dependent patterns of gene expression would represent the "address" or positional identity of the cell.
Morphogen gradients have been shown to incorporate a range of mechanisms including short-range signal activation, transcriptional/translational feedback, and temporal windows of target gene induction.
Among the main morphogens that play a critical role in cell–cell signals in both development and disease, we found members of the Wnt family, fibroblast growth factor (Fgf), hedgehog (Hh), transforming growth factor beta (TGFb), and retinoic acid (RA).
Do not confuse a morphogen with morphogenesis. Morphogenesis is the process by which structures form during development, reflecting different types of cell behaviour.
Read the book chapter "The developmental mechanics of cell specification" for a deeper understanding of this topic.
8. Segmentation and homeotic genes
Segmentation
During development the establishment of an axis is often followed by the division of the axis into repetitive series of similar but independent developmental units.
Segments occurs in many species, from the obvious segmentation in the body of insects, to the rhombomeres and somites of vertebrate embryos. These segments can be considered as developmental compartments, in which the clonal expansion of a particular cell line is constrained.
How can a cell and its clonal descendants be confined to a specific compartment?
This may occur simply because there is a physical barrier to cell mixing, or compartments may be defined by patterns of gene expression in the absence of any obvious boundary.
Homeotic genes give cells their positional identity. Different combinations of homeotic genes are expressed in response to different morphogen concentrations.
The homeotic genes encode transcription factors that regulate downstream effector genes controlling differentiation and morphogenesis.
Homeotic mutations cause cells to be assigned incorrect positional identities, resulting in the development of regionally inappropriate structures.