What determines the fate of a cell with respect to differentiation?

Question

I have been reading about Townes and Holtfreter's work in 1955, in which cells are dissociated from a blastocyst in an alkaline solution then mixed together and spontaneously reaggregates based on type, so epidermal cells around the outside and neural plate cells in the middle.

I understand enough about cell adhesion to understand why the cells will seem to attract cells of their own type, but would like to know how they can initially detect what to become and where they are needed in a specialised form, without something acting like a brain telling them what to become and where to go.

If the selection from the available types is random, as I suspect, what happens to blastocysts with too much epidermal tissue or vice versa? I'm struggling to imagine how organisms like this can develop without something taking the lead and actively coordinating what goes where.

Answer 1

Cell differentiation, cell fate and cell mapping is an interplay of accessible evolutionary strategies/programmes and responses to dynamic environmental cues such as specialized hormones (e.g. morphogens) and physical parameters and constraints. That is putting it very broadly. It is a complex issue, if L. Wolpert's PLOS assays are any indication. I compiled a few links to get you started.

Specifically, reappraising the topic of your cited classical experiment are R.Moore et al:

The classical cell sorting experiments undertaken by Townes and Holtfreter described the intrinsic propensity of dissociated embryonic cells to self-organize and reconcile into their original embryonic germ layers with characteristic histotypic positioning. Steinberg presented the differential adhesion hypothesis to explain these patterning phenomena.....

(Source: Robert Moore, Kathy Q. Cai, Diogo O. Escudero, Xiang-Xi Xu, Cell Adhesive Affinity Does Not Dictate Primitive Endoderm Segregation and Positioning During Murine Embryoid Body Formation, Genesis. 2009 September; 47(9): 579–589)

Regarding: ...without something taking the lead and actively coordinating...

On a hunch that you are not talking about complexity, attractors and polarity, I would like to share a few words. You may completely disregard them if you'd like.

My personal experience (from my country) is that few biologists delve into "that" branch of EvoDevo, because a profound understanding involves calculus, modeling and a knack for theoretical biology. Yet, afaik few struggled comprehending the evolutionary logic of making an organism based on Albert's book chapters alone.

See:

• Reaction–diffusion system
• Cell fate determination
• Fate mapping
• Asymmetric cell division
• Pattern formation
• Alberts Molecular Biology of the Cell describes this very well (can be accessed online for free)

I personally recommend G.Müller's authored/coauthored papers:

(open access) http://homepage.univie.ac.at/gerhard.mueller/publications-papers.html

Disclaimer: I am not specialized in the field of EvoDevo or Theoretical Biology.
Views expressed here are my own.

Answer 2

I would like to add to Lo Sauer's nice answer but give a slightly different perspective.

What you referred to as the "brain" of the cell, is mostly its regulatory program. An abstract way to think about the regulatory program is like a computer, or mathematical function, which gets input (in the form of signal molecules inside and outside the cell) and calculates an output (behavior - which genes/proteins to activate, for example) based on this input. This is usually how cells make decisions, both in differentiation and when reacting to the environment.

Of course the really interesting part is how the regulatory program is implemented. It seems that most of it is encoded in the DNA, although there is also a significant role for epigenetics factors (non-DNA factors that are inherited from the zygotes). As you can imagine this regulatory program is highly complex and is being studied by many groups, mostly using genomic experimental and computational techniques. It is currently far from being understood at a comprehensive level.

You can read about specific simple examples in some of the places Lo Sauer mentioned, for example Drosophila embryo segmentation/pattern formation.