A neuroblast is a dividing cell that will develop into a neuron often after a migration phase. Neuroblasts differentiate from neural stem cells and are committed to the neuronal fate. The main difference between a neuroblast and a neuron is the ability to divide; neuroblasts can still undergo mitosis, whereas neurons are postmitotic.
Neuroblasts are mainly present as precursors of neurons during embryonic development, however, they also constitute one of the cell types involved in adult neurogenesis. Adult neurogenesis is characterized by neural stem cell differentiation and integration in the mature adult mammalian brain. This process occurs in the dentate gyrus of the hippocampus and in the subventricular zones of the adult mammalian brain. Neuroblasts are formed when a neural stem cell, which can differentiate into any type of mature neural cell (i.e. neurons, oligodendrocytes, astrocytes, etc.), divides and becomes a transit amplifying cell. Transit amplifying cells are slightly more differentiated than neural stem cells and can divide asymmetrically to produce postmitotic neuroblasts or glioblasts, as well as other transit amplifying cells. A neuroblast, a daughter cell of a transit amplifying cell, is initially a neural stem cell that has reached the "point of no return." A neuroblast has differentiated such that it will mature into a neuron and not any other neural cell type. Neuroblasts are being studied extensively as they have the potential to be used therapeutically to combat cell loss due to injury or disease in the brain, although their potential effectiveness is debated.
In humans, neuroblasts produced by stem cells in the adult subventricular zone migrate into damaged areas after brain injuries. However, they are restricted to the subtype of small interneuron-like cells, and it is unlikely that they contribute to functional recovery of striatial circuits.
The characterisation of neuroblasts and their development in Drosophila melanogaster was widely achieved by Chris Doe, Corey Goodman and Mike Bate.
Neuroblasts development in Drosophila
In the neuroectoderm, small clusters of equivalent cells acquire the potential to become neuroblasts, through the expression of proneural genes. From there, one particular cell from each cluster is selected to become a neuroblast, through the action of the Notch signaling pathway. Once the future neuroblast cells are selected, they delaminate, then carry on dividing for a pre-programmed number of divisions.
Neuroblasts divide asymmetrically at every stage, creating one cell that continues being a neuroblast, and one cell that becomes the Ganglion Mother Cell (GMC), which goes on to divide into 4 differentiated cells (neurons or glia). The switch from pluripotent neuroblast to differentiated cell fate is facilitated by the proteins Prospero, Numb, and Miranda. Prospero is a transcription factor that triggers differentiation. It is expressed in neuroblasts, but is kept out of the nucleus by Miranda, which tethers it to the cell basal cortex. This also results in asymmetric division, where Prospero localizes in only one out of the two daughter cells. After division, Prospero enters the nucleus, and the cell it is present in becomes the GMC.
Each neuroblast goes on to create a specific sequence of cells with particular identities. This is partly based on the position of the neuroblast along the Anterior/Posterior and Dorsal/Ventral axes, and partly on a temporal sequence of transcription factors that are expressed in a specific order as neuroblasts undergo sequential divisions.
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- Liu, F; You, Y; Li, X; Ma, T; Nie, Y; Wei, B; Li, T; Lin, H; Yang, Z (April 2009). "Brain Injury Does Not Alter the Intrinsic Differentiation Potential of Adult Neuroblasts". The Journal of Neuroscience. 29 (16): 5075–5087. doi:10.1523/JNEUROSCI.0201-09.2009. PMID 19386903.