section_path: Development
section_name: Development
paragraph_text: Development
  
  In vertebrates, landmarks of embryonic neural development include the birth and differentiation of neurons from stem cell precursors, the migration of immature neurons from their birthplaces in the embryo to their final positions, outgrowth of axons from neurons and guidance of the motile growth cone through the embryo towards postsynaptic partners, the generation of synapses between these axons and their postsynaptic partners, and finally the lifelong changes in synapses which are thought to underlie learning and memory.
  
  All bilaterian animals at an early stage of development form a gastrula, which is polarized, with one end called the animal pole and the other the vegetal pole. The gastrula has the shape of a disk with three layers of cells, an inner layer called the endoderm, which gives rise to the lining of most internal organs, a middle layer called the mesoderm, which gives rise to the bones and muscles, and an outer layer called the ectoderm, which gives rise to the skin and nervous system.
  
  In vertebrates, the first sign of the nervous system is the appearance of a thin strip of cells along the center of the back, called the neural plate. The inner portion of the neural plate (along the midline) is destined to become the central nervous system (CNS), the outer portion the peripheral nervous system (PNS). As development proceeds, a fold called the neural groove appears along the midline. This fold deepens, and then closes up at the top. At this point the future CNS appears as a cylindrical structure called the neural tube, whereas the future PNS appears as two strips of tissue called the neural crest, running lengthwise above the neural tube. The sequence of stages from neural plate to neural tube and neural crest is known as neurulation.
  
  In the early 20th century, a set of famous experiments by Hans Spemann and Hilde Mangold showed that the formation of nervous tissue is "induced" by signals from a group of mesodermal cells called the organizer region. For decades, though, the nature of neural induction defeated every attempt to figure it out, until finally it was resolved by genetic approaches in the 1990s. Induction of neural tissue requires inhibition of the gene for a so-called bone morphogenetic protein, or BMP. Specifically the protein BMP4 appears to be involved. Two proteins called Noggin and Chordin, both secreted by the mesoderm, are capable of inhibiting BMP4 and thereby inducing ectoderm to turn into neural tissue. It appears that a similar molecular mechanism is involved for widely disparate types of animals, including arthropods as well as vertebrates. In some animals, however, another type of molecule called Fibroblast Growth Factor or FGF may also play an important role in induction.
  
  Induction of neural tissues causes formation of neural precursor cells, called neuroblasts. In Drosophila, neuroblasts divide asymmetrically, so that one product is a "ganglion mother cell" (GMC), and the other is a neuroblast. A GMC divides once, to give rise to either a pair of neurons or a pair of glial cells. In all, a neuroblast is capable of generating an indefinite number of neurons or glia.
  
  As shown in a 2008 study, one factor common to all bilateral organisms (including humans) is a family of secreted signaling molecules called neurotrophins which regulate the growth and survival of neurons. Zhu et al. identified DNT1, the first neurotrophin found in flies. DNT1 shares structural similarity with all known neurotrophins and is a key factor in the fate of neurons in Drosophila. Because neurotrophins have now been identified in both vertebrate and invertebrates, this evidence suggests that neurotrophins were present in an ancestor common to bilateral organisms and may represent a common mechanism for nervous system formation.