Specification of neurons
Signals from the mesoderm induce the neuronal fate. In other words, the mesoderm (middle part of the cell structure) tells cells to become neuronal cells. However, whilst all those cells have been given the signal and are all competent of becoming neuronal cells, this does not mean they will become neural cells. Lateral inhibition is where cells compete to adopt the neural fate. Cells express delta (ligand) and notch (receptor) to induce a proneural fate or ectodermal fate (skin and glial cells). Following lateral inhibition is delamination. Delamination is where a cell splits off in the embryo, for example, when a neuroblast (stem cell) splits off from the neuroectodermal sheet.
Cell lineage is determined by asymmetric localisation of mRNA and proteins, in other words this tells us what the stem cell should develop into. A stem cell divides and produces a copy of itself (to continue making more cells) and produces a ganglion mother cell. Ganglion mother cells can divide to give rise to neurons and glial cells.
There are 3 broad types of neurons: sensory cells, interneurons and motor neurons. As we previously said, Neuroblasts are stem cells, however, they age. With ageing, they express different genes (genes encoding different transcription factors included), thus they have different competency. Timing is highly important for gene expression. Ganglion mother cells, which too vary in competency, can become young or mature neurons which will climb radial glia. Radial glia are progenitor cells (cells which have a tendency to differentiate into a specific type of cell.) When the neurone is produced, it makes a difference as the age of when the cell last divides determines which layer of the cell if will enter. Younger cells migrate up the radial glial migrate to the periphery, and must go past older neurons (ones that differentiated earlier). As they migrate past older ones, they express new transcription factors as a result of retinoic acid signals secreted by earlier born cells.
Neuronal diversity is determined by a generation of chemical gradients. On both sides of the cells there are organisers of the neural tube, called the roof plate and floor plate. On the roof plate (the dorsal side), bone morphogenetic protein (BMP) circulates. This gives rise to neural crest cells and sensory neurons. Neural crest cells are cells which make up the peripheral nervous system. On the ventral side with the floor plate, sonic hedgehog protein (SHH circulates) which is made from the notochord. SHH gives rise to V1 and V2 interneurons and motor neurons.
So, BMP and SHH tell us what type of cell to become, but how do these cells know where to go and what to innervate. For example, we have a motor neuron, but is it going to be a motor neuron to work in the brain, innervate a skeletal muscle, or work in the heart? Anterior-posterior positioning of proteins produced by Hox genes determine this. Hox genes are a group of related genes that specify regions of the body plan, there is a combinatorial code of hox genes.