How does a cell know when to stop dividing?

Peter Ashby p.r.ashby at dundee.MAPS.ac.uk
Mon Jan 25 16:12:37 EST 1999

In article <36aca809.10547383 at news.cis.yale.edu>, mapson at mapson.com
(Mapson) wrote:

> On Fri, 22 Jan 1999 19:38:10 +0100, p.r.ashby at dundee.MAPS.ac.uk (Peter
> Ashby) wrote:
> >Are you asking how form is arrived at in the embryo or are you asking how
> >do structures stop growing? These are two very different questions and
> >therefore have very different answers.
> I guess I'd like to know both, since they would describe useable
> strategies.
> The embryo, being less about form maintanence and more about pure form
> growth, sounds like the simpler scenario (but then, I am not a
> biologist). The ultimate question from my lay perspective, however,
> seems to be "how does a a single fertilized egg eventually, through
> division and other processes, end up being *positionally* in place to
> become a cell on the tip of my finger (valve in heart/cell in
> brain/etc.), and how (when such a cell dies), does a nearby cell know
> just how much growth (and what direction of growth) is required  to
> replace(or ignore, if locally appropriate) it so as to functionally
> maintain overall form." I mean by positionally that I am not
> interesting in cellular functional differentiation of cells per se,
> but only in how any cell comes to be in its "resting spot", be it in
> an artery or in an eye.
> The conceptual problem from my point of view is that it would seem
> necessary for some kind of 3-d "template" to guide growth resulting in
> the sort of unbelievable precision we see in living things. But I
> don't know of any scientific theories suggesting such. What do I mean
> by template? Well,  perhaps some sort of ever-extending  weak
> bioelectric field is exerted by cells, following a design pre-wired in
> our DNA. Would be kind of like biological "scaffolding." 
> Point is, there is no apparent central point from which the cells are
> "graphing" themselves on to the 3D form with measurements, and I am
> not aware of what other mechanism they might be using to find their
> resting places. Even without a "central reference point", it would
> still seem that there has to be a way that a cell is communicated data
> on its position in reference to some scaling of it's overall form. 
Cells in an embryo do have a sense of where they are in 3D space. they are
informed of this by surrounding structures which release signals that
inform cells of their position (and often also specify their fate). This
system is set up in embryos in two different ways, in some embryos (frogs
for eg. or flies) the egg cell has polarity curtesy of the mother and so
you have a chicken and egg situation. In other embryos, notably mammals
there is no detectable polarity in the egg and the developing cell mass
needs some other way to know which way is up. This may come from the
process of uterine implantation or it may be random but whichever way a
group of cells become a signalling centre and the embryo has a front end
(eg close to the centre) and a back end (eg far from the centre). once you
have  front and back you have a right and left and a top and bottom drop
in as well or are specified by the direction away from say the yolk. I
study the limb so I will describe the situation there. Proximal and distal
(shoulder to finger) is driven by the ectoderm (skin) at the tip of the
growing limb bud, this also regulates growth, remove it and growth stops.
Anterior and posterior (thumb to little finger) is signalled by
specialised region at the posterior edge called the zone of polarizing
activity (ZPA). When transplanted to the anterior edge of the limb bud a
mirror image duplication results. This region secretes a potent signalling
protein called sonic hedgehog. Up and down (back of the hand to the palm)
is signalled by the rest of the ectoderm as when you rotate the ectoderm
on as thoug it were a jacket you reverse up down polarity.

So cells do have sense of where they are in 3d space and they act (switch
on and off the appropriate genes) accordingly. The whole thing is hard
wired by the dna but once set in motion an embryo can do a lot without
minute directions from genes. The genes seem to set conditions in groups
of cells and then let them run. Hell it seems to work, even if we don't
fully understand how. But then LIFE the program was a bit like that too.


Peter Ashby
Wellcome Trust Building
University of Dundee
Dundee, Scotland
Reverse the spam and remove to email me.

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