GENES
involved in neural development
Some Common Genes become Specialized to the Neural Tissues
Embryonic stem (ES) cells are converted to midbrain neurons through the
induction of OTX homeobox genes (OTX1 and OTX2). OTX2 is expressed throughout
the cells of the body earlier in development, but is later restricted
to the anterior portions, where a large majority of the neural development
in the body takes place. OTX1 is expressed in the neuralectoderm of the
dorsal telencephalon, which later forms the cerebrum of the adult brain.
Common Developmental Genes are Quite Active in Neural Differentiation
There are many other genes which have been found to function in neural differentiation. Genes such as Pax2, Pax5, Wnt1, En1, and Nurr1 have been found to control the differentiation of dopaminergic (link to parkinson’s) and serotonergic neurons in the midbrain and hindbrain. Dopaminergic neurons have also been found to have other genetic factors in control of their differentiation and development. The Sonic hedgehog (Shh) gene was found to work in tandem with FGF8, and ascorbic acid to increase the number of tyrosine hydroxylase-positive (TH+) dopaminergic cells. Shh has also been found to help in the differentiation of the hindbrain serotonergic neurons. The photo below partially describes the process in which TH+ cell precursors are kept in a proliferative stage and then released to differentiate. (24)
(A) ES cell progeny at stage 4 express nestin, an intermediate filament protein expressed in CNS stem cells but not in neurons and glia (scale bar = 20 m). (B) ES cell progeny at stage 5 differentiate into TH+ neurons. Removal of the mitogen initiates differentiation of the nestin-positive cells into neurons recognized by the antibody TuJ1 that binds to a neuron-specific tubulin. A subset of the neurons expresses the enzyme tyrosine hydroxylase (TH), which is required for the production of catecholamine neurotransmitters (scale bar = 20 m). (C) The effect of HEPES buffer on differentiation of TH+ cells. N3FL is a medium used for ES culture10. (Caption from source)