Instant Notes - Key concepts


1. Development

1.3. Mechanisms of Cell Commitment

In animal development two main mechanisms are used for cell commitment to initiate a series of events that eventually result in cell differentiation: 
  • Inheritance of cytoplasmic determinants (intrinsic- lineage related) 
  • External inductive signals (extrinsic - context related).

Cytoplasmic determinants 
A cell can divide to produce 2 daughter cells committed to different fates, and this can be due to intrinsic information inherited from the mother cell during cell division. Indeed asymmetric distribution of cytoplasmic regulatory factors necessary for specification (e.g.  mRNAs and proteins such as transcription factors) can influence the fate of the daughter cells. 
Asymmetric distribution of cytoplasmic determinants results in asymmetric cell division, a condition that frequently occurs in early development in invertebrate embryos (e.g. Drosophila) when maternal gene products, localized to particular egg regions, are asymmetrically distributed to different blastomeres during cleavage. 

Inductive signals
Induction is an extrinsic process that depends on the position of a cell in the embryo, i.e. information instructing the cell to follow a certain fate is received from the environment surrounding the cells. Induction implies cell-cell communication; it 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. For instance, 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. 
What is the nature of the inductive signals?
The inductive signals are often proteins released from one cell type that can interact with receptors on the surface of responding cells or pass the cell membrane (e.g. Retinoic Acid, a derivative of Vitamin A - Retinol) and interact with intracellular receptors. 
How do they act?
The binding of the inductive signal with receptors on the target cell membrane initiates a signal transduction cascade that influences the activity of transcription factors and/or other proteins eventually regulating target gene expression. Inductive signals that interact with intracellular receptors act as ligand-dependent transcription factors.
Response to an inductive signal can be stereotyped, or graded. In the case of a graded response (i.e. dependent on the inductive signal concentration), the inductive signal acts as a morphogen. 
The response to specific inductive signals depends on the competence of the receiving cell (i.e. the ability to receive the signal and to react in an appropriate manner through the appropriate cell surface receptors, signal transduction apparatus, or downstream target transcription factors). The loss of competence is one mechanism by which a cell becomes "irreversibly" committed (i.e. determined) to a given developmental fate by loosing the ability to respond to other inductive signals that drive towards alternative fates.
Two types of induction can be distinguished:
  1. Instructive induction: the responding cell has a choice of fates and is instructed by the Inducer to follow one specific developmental pathway that is alternative to the one followed in the absence of inductive signals or in presence of different concentration of the same signals or different signals. 
  2. Permissive induction occurs when the responding cell is already committed to a certain fate (contains all the potentials that are to be expressed), and requires a permissive environment to enable the developmental pathway to be expressed. When the signal reaches a threshold concentration the cells can make only one kind of response which is determined by their developmental history.

As development proceed there is a continuous of inductive processes ranging from strongly instructive to fully permissive.