How do cells know what to be?

We can think of living organisms such as human beings as complex machines that are designed to do multiple jobs such as walking down the street, watching their favorite movie or adding the prices of things in a grocery shop. The basic building blocks of this complex machine are cells of different types. Organisms use cells of different types such as muscle cells, neurons, skin cells to do these jobs. Otherwise it would be similar to building a complex machine just with a single part and that too of the same size. However, all of the different cells originate from a single fertilized nucleus and carry the necessary genetic information in their DNA.

There are multiple ways cells determine their fate. In this article, we will discuss one of them.

Cells often establish their identity based on positional information i.e. where they are situated¹. How do Cells know where they are? They understand it based on the amount of some factors (known as morphogens²) in the cell. Let’s try to understand this with a toy example. Let us assume our living organism to be a square box. The square box goes through 4 rounds of division to create 2⁴=16 cells (smaller square boxes). In this square box concentration of one factor (M1, marked in red) decreases from right to left and the other factor (M2, marked in blue) decreases from top to bottom (Fig. 1a). Now when the cells divide into 16 cells, each of them have different amounts of M1 and M2 based on where they are. What does it have to do with determining the cell types?

Before answering that, let’s revisit the central dogma of biology. During cell division, cells pass on their genetic information encoded by base pairs A,T, G, and C by replicating its DNA. The useful information of the DNA encodes into mRNA by the process of transcription. Through the process of translation mRNAs produce proteins, which ultimately give cells their functionality. The molecules such as M1 and M2 interfere with transcription (transcription factors). Sometimes, they are necessary for the transcription of some genes to happen (promoter) and often they don’t let transcription happen (inhibitor). Let us assume our toy organism expresses two genes G1 and G2. G1 expresses only when M1 is high (Fig. 1b) and G2 expresses when M2 is low (Fig. 1c) and we get this 16 cell organism to distinguish into 4 cell types (Fig. 1d). Similarly one can have up to 2ⁿ cell types if the organism expresses n genes.

Reality is generally more complex. The geometry is often more complicated than that of a square, there are more than two transcription factors, more than two genes, and gene products themselves often act as transcription factors for other genes. For example, in a fruit fly embryo, we show the concentration gradient created by three morphogens (similar to M1, M2) (Fig. 1e) and region of expression of a few genes (similar to G1, G2) (Fig. 1f) out of many more and one can imagine this comparatively simple organism distinguishes itself into how many cell types³,⁴. Going back to our toy organism, you may be further interested to know how the pattern of M1 and M2 establishes in the square box in the first place, which you can read in (5) or it can be the topic of another YSEA.

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