July 12, 2006 -- New Haven, Conn. — The fate of cells that go on to form the face, skull
and nerve centers of the head and neck in vertebrates is determined
much earlier in development than previously thought, and is independent
of interaction with other forming tissues, according to a recent study
published in the journal Nature.
collaborators at Yale and Caltech demonstrate with three different
technologies — immunostaining of proteins, in situ hybridization and
multiplex RT-PCR of mRNAs — that formation of neural crest cells in
chick embryos is independent of both mesoderm and neural tissues. They
also identify, Pax7, as an early marker of neural crest formation and
prove that its function is required in the earliest stages of
The neural crest is a population of stem cells that migrate extensively
during development and give rise to many derivatives, including most of
the bone and cartilage of the head skeleton, pigment cells of the skin,
and cells of the peripheral nervous system.
In humans, cleft
palate, heart valve malformations and various tumors are among the
common malformations associated with disruption of neural crest
Chick embryos have well-characterized stages and
are a valuable model for examining vertebrate development. While it was
known that the ability to form neural crest cells declines after "stage
10," the researchers were seeking the earliest conditions surrounding
formation of these important stem cells.
origin of neural crest cells — where, when and how they arise — is a
critical step if we are to manipulate them for therapeutic purposes,"
said Martín García-Castro, assistant professor of molecular, cellular
and developmental biology at Yale and principal investigator on the
study. "Implications of these basic questions of biology and
development reach far beyond these chicken and eggs."
work from the 1940's before molecular tools were available, the neural
crest was thought to form by interactions between neural and non-neural
cell layers. "We show in this work that neural crest stem cell
precursors are designated very early in development — as early as the
gastrula stages — and in an independent fashion from those other
tissues," said Martín García-Castro.
The researchers grew grafts
of cells from "stage 3" chick embryos, before the neural plate formed,
in non-inducing cultures. Surprisingly, restricted regions of the
embryo generated both migrating neural crest cells and their derivative
cell types, without any interaction with neural or mesodermal tissues.
results are contrary to current text-book models and suggest that
different modes of neural crest induction operate during development,"
said Martín García-Castro. "Interestingly, the one we have uncovered is
related to the early, cranial neural crest cells, the only ones in
higher vertebrates that retain bone and cartilage forming potential."
Source : Yale University