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The relation between Determination and Differentiation

by Felix Brehar, felix_brehar@yahoo.com 

[click on pictures below to get more detailed view]

To explain certain phenomenon which appear during the first stages of ontogenesis, we must introduce the notion called cellular determination The state of determinate cell is an intermediate one, which follows to the state of a pluripotent cell and which precedes the state of differentiated cell. In the first stage appears two types of determined cells: type A and type B, which are not different from a morphological point of view but only because of the potential of activation of two different sets of genes. For instance, cell A according to the previous theory, contains the type one of nonhistonical active protein. This will activate the gene a, which synthesize receptors of membrane and soluble receptors in the extra cellular space and the gene b, which synthesize another type of inactive nonhistonical protein (II) (Fig.4). In the following stage the cells of type A, spread in the cellular population, which has resulted from the repeated divisions of the pluripotent cells, will migrate one to another (on the base of receptors). As the cells of type A interaction, the activation of receptors of membrane determine the activation through specific mediators of nonhistonical protein synthesized initially (II). This will activate (Fig.4) the genes b and c, which will synthesize the specific proteins as well that gene e, which is responsible by its own synthesis. In this moment takes place the cellular differentiation. Now the cells of type A are different from the cells of type B (by morphological point of view) being grouped and forming a distinctive embryonic structure. Thus, a determinated cell has two variants (Fig.2):

1. As a result of interaction (through a direct contact or at a distance by help of soluble receptors) with the other cells of the same type (cell A with cell A and cell B with cell B) is initiated the process of cellular differentiation, forming a certain type of embryonic structure (or later a certain type of tissue);

2. If it is not realized this contact then the process of differentiation does not takes place and the determined cell may come back at the state of pluripotency, after some divisions, because the nonhistonical protein synthesized in the moment of cellular determination (Figure 4-I), does not intensify the gene which is reponsable by its own synthesis. But the nonhistonical protein intensified in the moment of cellular differentiation (Figure 4-II) does intensify the own synthesis, so the phenomenon of cellular differentiation becomes irreversible.
So, in this way, an important law of biology is reflected at the molecular level, namely the ontogeny is a short and quick revision of the ontogeny. The process of cellular differentiation is a sequential one and it is realized step by step, every realized stage making up the beginning for a new stage, and the activation of the divers sets of genes, which have appeared during the evolution in a chronological order, is based on this process.
I would add some more ideas about this theory:
- The most probably localization of the X site is on the X chromosome (only one X chromosome is an active chromosome; the other one is the Barr corpuscle)
-Now, when the human genetic map is finished, it is a way to verify the validity of this theory. Let it compare the intron sequences of the specific tissue genes (for the muscular tissue genes which synthesize: actin, myosin etc.)If it is founded similar sequences only in this genes and not in the others,then the theory is partial confirmed.

How can maintain a cellular line a state of differentiation ?

In normal condition,a cellular line can maintain a differentiation state during the cellular multiplications,then nonhistonical protein must intensify, about the genes which are responsable by the morfofunctional specific features of the respective cellular line,also the gene which are responsible by its own synthesis(otherwise,that nonhistonic proteins arrive at a minimum concentration after some divisions).Thus it is created a phenomenon of a pozitive feed-back (Figure 3).

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URL: http://www.geneticengineering.org/ideas/brehar2.html
Version: 0001. Last update: 10 June 2001.
Copyright 2001 by Felix Brehar. All rights reserved.