Generation of neural
crest-derived peripheral neurons and floor plate cells from mouse and
primate embryonic stem cells
Mizuseki K, Sakamoto T, Watanabe K, Muguruma K, Ikeya M, Nishiyama A,
Arakawa A, Suemori H, Nakatsuji N, Kawasaki H, Murakami F and Sasai Y
Proc Natl Acad Sci U S A 100(10):5828-33 (2003)
SUMMARY
To understand the range of competence of embryonic stem (ES) cell-derived
neural precursors, we have examined in vitro differentiation of mouse
and primate ES cells into the dorsal- (neural crest) and ventralmost (floor
plate) cells of the neural axis. Stromal cell-derived inducing activity
(SDIA; accumulated on PA6 stromal cells) induces cocultured ES cells to
differentiate into rostral CNS tissues containing both ventral and dorsal
cells. Although early exposure of SDIA-treated ES cells to bone morphogenetic
protein (BMP)4 suppresses neural differentiation and promotes epidermogenesis,
late BMP4 exposure after the fourth day of coculture causes differentiation
of neural crest cells and dorsalmost CNS cells, with autonomic system
and sensory lineages induced preferentially by high and low BMP4 concentrations,
respectively. In contrast, Sonic hedgehog (Shh) suppresses differentiation
of neural crest lineages and promotes that of ventral CNS tissues such
as motor neurons. Notably, high concentrations of Shh efficiently promote
differentiation of HNF3β(+) floor plate cells with axonal guidance activities.
Thus, SDIA-treated ES cells generate naive precursors that have the competence
of differentiating into the "full" dorsal-ventral range of neuroectodermal
derivatives in response to patterning signals.
LINK
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12724518