**The Famous Spemann Organizer** In the 1930's, Mangold and Spemann discovered neural induction during experiments in which they transplanted small pieces of tissues from one amphibian embryo to another at pregastrulae stages. The key observation was made when they transplanted a small piece of tissue from a region called the dorsal blastopore lip (DBL), and the host embryo responded to the grafted tissue by forming a complete secondary dorsal axis. Importantly, most of the tissues in the secondary dorsal axes were not derived from the transplanted tissue but rather from the tissue in the host embryo. In particular, the secondary dorsal axis contained a complete nervous system that was derived entirely from the ventral ectoderm of the host embryo, a tissue that would have differentiated into skin in the absence of a graft. The implication of this observation was that the transplanted tissue can act as a source of inducing signals that can cause ventral ectoderm to form neural tissue, and that this inductive interaction normally occurs on the dorsal side of the embryo. Tissues in the DBL was later termed the **organizer** because of its ability, when transplanted, to reprogram the ventral side of the embryo to form dorsal tissue, not only in the ectoderm but also in the internal mesodermal tissues. Following Mangold and Spemann's lead, it was subsequently found all vertebrate embryos appear to contain a region, called **Spemann's organizer**, which can induce ectoderm to form neural tissue. **Anterior-Posterior (AP) Patterning** The neural plate is a morphologically homogeneous sheet of epithelial cells derived from dorsal ectoderm, which acquires its neural potential and fate as a result of inductive signaling. As the neural plate rolls up and closes into a tube, a series of constrictions appear in its wall, subdividing the anterior end of the tube into a series of vesicles representing the anlagen of fore-, mid- and hindbrain. Further subdivision ensures, most conspicuously in the hindbrain region (rhombencephalon), where a series of segment-like swellings, rhombomeres, are formed. Caudal to the hindbrain, the neural tube forms a long narrow cylinder that is the precursor of the spinal cord. These early morphological features of the neural tube dictate the overall plan of the CNS and predict its later regional specializations. The neuroepithelium then commences with the production of a huge diversity of region-specific cell types, each having a distinct identity in terms of morphology, axonal trajectory, synaptic specificity, neurotransmitter content, and so on. Different neuronal cell types also carry distinctive surface labels that may ensure accuracy of axonal navigation and the formation of appropriate connections with other cells. Perhaps most strikingly, individual neurons or groups of similar neurons originate at predictable times and at precise positions within the various regions of the neural tube. In some cases, neurons remain in their position of origin during and following differentiation; in other cases, young neurons or their precursors are directed to migrate along stereotypic paths to settle in locations distant from their position of origin. Correct specification of this intricate spatial ordering, or pattern, of cells is crucial to later events in CNS development when neurons establish complex arrays of specific interconnection that constitute functional networks. Activity-dependent processes and regressive events, such as the pruning of axons and cell death, later reinforce and refine initial patterns of connectivity, but a high-degree of precision is achieved from the outset, dependent on, and as a direct result of, appropriate cell patterning. **AP Polarity** The initial establishment of AP polarity along the neuraxis is coupled intimately to the establishment of the main body axis during early embryonic development. Although AP axis formation in the vertebrate embryo remains poorly understood, it may have conceptual similarities with the strategies used for axis determination in the Drosophila embryo, where genetic studies have produced a detailed understanding. I Drosophila, AP polarity is first established by a gradient of positional information produced by the maternal morphogen Bicoid emanating from the anterior pole of the egg. The gradient of the Bicoid transcription factor initiates a cascade of transcription factor activation that progressively subdivides the body axes further into smaller segmental units. **Neural Induction** AP patterning of the CNS begins during the process of neural induction as dorsal ectoderm takes on a neural fate. This process divides nascent neural tissue into prechordal (anterior) and epichordal (posterior) neural plate regions based on signals that come from adjacent head and tail organizing tissues. Formation of the prechordal plate requires two inhibitory signals produced by the head organizer: one that inhibits BMP and the other WNT signaling. Tail organizer tissue produces potent posteriorizing agents, including WNTs, FGFs and RA. The extent of signals required for generating AP polarity, however, is not fully known and the details of their action remain to be explored. Interestingly, both neural and anterior-neural are default states, requiring specific molecular activity to become non-neural (BMP) or posterior-neural (WNT). Following the establishment of polarity along the AP axis of the embryo and the delineation of prechordal and epichordal regions of the neural plate, the AP axis becomes further regionalized into smaller and smaller domains, as revealed by the expression of developmental control genes. This process of progressive regional refinement involves two general classes of mechanisms - the establishment of local organizers as sources of diffusible factors (morphogens) that inform neighboring cells about their position and fate, and the partitioning of the neuroepithelium into small modules or segments in which development can proceed with a degree of autonomy. IN both cases, a conspicuous and important feature is the setting up of boundaries, which position a local organizer, contain cells within a compartment, or both. **The Notochord** It is a **ventral organizer**. Crucially involved in patterning the ventral neural tube is the notochord, a mesodermal skeletal structure that occupies the midline of the embryo directly beneath the neurectoderm. Grafting experiments in avian embryos have shown that both floor plate and motor neuron differentiation depend on notochord signals. Early removal of the notochord results in a normal-sized spinal cord in which both of these ventral cell types are absent, with dorsal cell types and dorsal specific markers appearing in their place. Similarly, implanting a supernumerary notochord alongside and in contact with the lateral neural plate results in formation of an additional group of floor plate cells at the point of contact, with clusters of motor neurons on either sides. These experiments show not only the power of the ventral midline signal to influence fate choice, but also the multipotent competence of responding neural tube cells at different DV positions. At a slightly later developmental stage, the floor plate itself acquires the same inductive capabilities -- it can also induce motor neurons and will induce itself homeogenetically. The floor plate thus becomes an organizing center for a ventral pattern that is built into the neural tube itself. **Dorsal Blastopore Lip (DBL)** The Dorsal Lip of the Blastopore is a structure that forms during early embryonic development and is important for its role in organizing the germ layers. The dorsal lip is formed during early gastrulation as folding of tissue along the involuting marginal zone of the blastocoel forms an opening known as the blastopore. It is particularly important for its role in neural induction through the default model, where signaling from the dorsal lip protects a region of the epiblast from becoming epidermis, thus allowing it to develop to its default neural tissue.