Neurulation and the Notochord:
(Image 5 - signals involved in neural induction)
Neural induction occurs throughout gastrulation, and is concurrent with dorsal-ventral axis patterning. Pluripotent cells undergo several stages before they reach the neural precursor stage - Neural ectoderm is induced mainly by the inhibition of BMP (BMP-4 in xenopus) by secreted signals from the organizer such as Noggin, Chordin or Follistatin which inhibit BMP signaling. Neural induction in fact requires no signaling - it is the epidermis fate of the ectoderm that requires BMP signaling to be induced. BMP also affects the mesoderm, and specifies the non-dorsal mesoderm - i.e. the lateral and intermediate mesoderm.
Throughout gastrulation, the organizer is patterning the future anterior-posterior axis of the neural tube, in ways that change as gastrulation progresses. For example, secreted Cereberus induces head formation (even ectopically) by inhibiting BMP + Wnt. Other head-inducing proteins are Frzb, Dickkopf which both inhibit Wnt signaling, and Insulin-like growth factors, which block the BMP and Wnt signaling pathways inside the cell. Induction of the trunk and posterior embryo seems to mainly rely on a Wnt, BMP and Nodal gradient, and the presence of retinoic acid.
The dorsal mesoderm or organizer becomes the notochord during gastrulation, as already explained, via involution. The notochord very quickly differentiates once it has involuted - it elongates via convergent extension from the cluster of cells in the Spemann organizer, forming a thin rod of cells. The notochord induces the overlying ectoderm - the neural plate - to begin neurulation.
Neurulation can occur in 2 ways: primary neurulation involves formation of the neural tube, via structural changes in the neural plate, whereas secondary neurulation involves the formation of a neural tube from mesenchymal migration. Both of these processes can occur in the same species, and primary neurulation usually forms the anterior neural tube, whereas the posterior is formed by secondary neurulation. Closure of the neural tube occurs in different ways in different species - it can either be initiated in one place i.e. the junction between the mid and hindbrain as in birds, or via several sites, leaving holes called neuropores, which close at different times as in humans. These sections then join, forming a complete tube. We will consider neurulation in the chick and mammals here.
Primary neurulation begins with the formation of the neural groove and neural folds via bending of the neural plate: bending begins when the notochord sends signals up to induce the ectoderm to change into the long, thin neural plate cells. The neural plate then elongates via convergent extension along with the notochord as it differentiates. The elongated cells attach to the notochord via Medial Hinge Point cells (MHP cells) formed from the site of the organizer. The MHP cells get smaller and become wedge-shaped - causing a hinge-like movement and the cells on either side bend upwards. Other hinge points form - helping form the neural groove. The ectoderm also extends inwards, pushing the neural plate up and in.
Primary neurulation continues when the folds close and separates from the ectoderm on either side. This is aided by the differential expression of CAMs - the neural folds express N-CAM and N-cadherin, whereas the ectoderm expresses E-cadherin.
(Image 6 - Primary neurulation. Sourced from Wikipedia commons)
The neural tube and beyond:
The neural tube goes on to form the fore, mid and hind brain, the spinal cord and precursor neural crest cells which form a variety of structures.
(Table 1 - The fates of neural crest cells) (Image 7 - Position of neural crest cells. Adapted from Wikipedia)
The neural crest cells migrate from the top of neural tube, from a region called the roof plate (shown in green on the diagram). This occurs at different times in different species. Neural crest cells have a very wide range of fates - cartilage, pigment cells, all of the neurons and glia of the peripheral nervous system, and more - this includes both ectoderm and mesodermal fates. They migrate when triggered by BMP signaling.
The neural tube differentiates into the 3 primary brain vesicles - the Prosencephalon, Mesencephalon and Rhombencephalon - or the fore, mid and hind brain. The vesicles form as bulges in the tube, and begin to form part way through the closure of the neural tube. The vesicles are then further divided into secondary vesicles which have finished forming by the end of the neural tube closure. The rhombencephalon develops in a segmental way - segments called rhombomeres, which have different developmental pathways, and from which the cranial nerves originate. After the secondary vesicles have formed, the brain is further altered by the secretion of a fluid called cerebrospinal fluid, which puts pressure on the tube and causes a large increase in volume.