hi,

i am looking for the gene responsible for head development in humans.
i don't want the genes that code for structures in the head such as
the sonic hedgehog gene etc. but rather that gene(s) which is
responsible for head development from the neck and above.

Hard question to answer succintly.

First, the Hox family of genes is necessary for setting up the A-P
axis. Hoxa2,3,8 are all needed in mice for normal development of the
head and brain. Also needed are Noggin, Chordin, and follistatin are
all needed to set up the neural plate. Neural tube closure requires
Pax3, sonic hedgehog and openbrain.  Bone-morphogenic-proteins, a
subset of the Transforming growth factor beta family, including BMP4
and 7 are also required for neuronal differentiation within the neural
tube. The epidermis which surrounds all of this requires TGFalpha and
Keratinocyte growth factor (aka FGF7) for development.  FGF8 yields
molars, BMP4 yields incisors.

Okay, i hope that conveys my point, there isn't one gene that codes
for head development.

The intricate and well timed cascades of signaling and inhibition
which result in further differentiation, signaling, and inhibition are
responsible for the head developement.


Just to clarify part of your question - SHH doesn't code for a
structure, it is part of a signaling pathway that leads to the
differentiation of structures.

Hope that helps, 

Patrick

thank you patrick for that very helpful reply. my question was based
on the reasoning that however complex the signaling pathway, there
must ultimately be one trigger that initiated the budding of the head
from the body. there must be a gene which codes for this. i understand
that experiments in mice and frogs have resulted in the inhibition of
head development. it is this triggering gene that i am looking for.
perhaps it has not been discovered in humans yet. i would settle for
as much info on the genetic pathway leading up to the head budding as
possible.

I think Patrick's point was that there is no one triggering event --
there are a myriad of interacting pathways that must all function
properly to create the incredibly complicated structure that houses
our intellect. Development is an intricate process -- there is not one
gene for arm budding, one for legs, one for head. If one genetic
mutation prevents proper head formation it doesn't mean that gene
triggers head development, it just means that that gene is one of the
ones that is required for proper head development.

ok, i accept there are many influencing factors in head development. i
am not an expert but i know for instance that in the xenopus embryo as
in other organisms, the spemann organiser is responsible for head
development. this tissue contains a few genes which play a part in
shaping this development. one of these genes is dickkopf1. a tadpole
embryo microinjected with inhibitory anti-dkk1 antibodies lacks
anterior head structures. could this gene also not provide a similar
function in humans?

the intention behind my question was to establish a mechanism for
inhibiting head development in the human embryo and thereby provide a
means of growing tissues, organs and limbs for transplantation.

if i have correctly identified dkk1 as a necessary factor in head
development the next question is to determine the mechanism of
inhibiting its function. a cumbersome method would be to inject the
embryo at the 2 week stage with anti-dkk1 antibodies or inject the
embryo with cdnas complimentary to the dkk1 gene.

i don't know your ethical stance on this procedure. but i eagerly
await your responce.

Dkk1-4 are present in humans, they are negative regulators of the
Wnt/Frizzeled/beta-catenin signaling pathway.   I meant to include it
in my original comment, however, I have not seen or read any account
of definitative human evidence of Dkk1's head organizing function. You
should also note that there is evidence supporting (not suprisingly)
further complexities in this pathway, which involve noggin
cosignaling. I think Dkk-1 is a fair target for your hypothesis
however.

With regards to inhibiting Dkk1, the antibody complex is a smart way
to go, as is siRNA.

You could also get really clever and do a temporally and spacially
controlled knockout using the Cre/Lox + tetracycline system.  It would
require some real careful gene expression assays, but could be a
really clever way to do what you are thinking.

As for the morals of it, I'm a bit of a crazy leftist, but to be
honest, I don't see the need for this sort of work, and it kinda makes
my stomach turn.  In addition, its really bad PR for the scientific
community.  Its something almost out of a horror novel for a lot of
people.  Progress is being made using SCNT to generate patient
specific and functional (in dogs and mice) kidneys, trachea, blood
vessels.  I think that as a scientific community we are much better
off staying away from the "developing embryo for tissue/organs". We
have other, what will prove to be more efficient means of developing
tissue.

Great Question!

-- Patrick

thanks for the excellent reply. don't you think that injecting say an
enucleated cow egg with the nucleus of the desired patient together
with cdna would lead to selective developmental inhibition. thereby we
may grow organs, tissues etc without the possibility of the egg ever
differentiating into a living human embryo. cdnas i suspect would be
replicated during the cell cycle.