Neural Induction and Notochord Development

Neural induction is the process by which a region of ectoderm is directed to become the neural plate, the primordium of the brain and spinal cord. It is driven by signals from the organizer and the axial mesoderm, especially the notochord — a transient midline rod that both patterns the early body axis and is the defining structure of the chordates.

Definition

Neural induction is the specification of neural plate fate in dorsal ectoderm by signals from the organizer and axial mesoderm; the notochord is the midline rod of axial mesoderm that arises from the organizer/node, patterns the neural tube and somites, and forms the embryonic axial skeleton.

Scope

This topic covers the formation of the notochord from axial mesoderm, the inductive signalling by which the organizer and notochord neuralize the overlying ectoderm, the default model of neural induction, and the role of the notochord in patterning the neural tube and axial skeleton. It is a reference account of developmental anatomy and does not provide clinical guidance.

Core questions

• How does the notochord form from axial mesoderm?
• How do the organizer and notochord induce the neural plate?
• What molecular signals underlie neural induction?
• How does the notochord pattern the neural tube and surrounding tissues?

Key concepts

• Organizer (Spemann-Mangold organizer; node in amniotes)
• Notochord and axial mesoderm
• Neural plate and neuroectoderm
• BMP antagonists (noggin, chordin)
• Sonic hedgehog and ventral neural tube patterning
• Notochord remnants (nucleus pulposus)

Key theories

Default model of neural induction

Ectoderm is intrinsically predisposed to a neural fate and is held in an epidermal state by BMP signalling; organizer-derived BMP antagonists such as noggin and chordin relieve this inhibition, allowing the underlying neural fate to emerge.

Mechanisms

The organizer (the dorsal lip in amphibians, the node in amniotes) gives rise to the prechordal plate and notochord, a rod of axial mesoderm running along the embryonic midline. The organizer and notochord secrete antagonists of BMP — including noggin and chordin — that locally inhibit BMP signalling in the overlying ectoderm; according to the default model, this relief from BMP inhibition allows the ectoderm to adopt its intrinsic neural fate and form the neural plate, which then folds into the neural tube. The notochord continues to pattern the developing neural tube and somites, in part by secreting Sonic hedgehog to specify ventral neural cell types and to induce sclerotome. The notochord itself is largely transient: it induces the vertebral bodies and persists in the mature spine only as the nucleus pulposus of the intervertebral discs.

Clinical relevance

Disturbances of neural induction and neural tube closure are linked to neural tube defects such as anencephaly and spina bifida, and persistent notochordal tissue is the developmental origin of chordoma, a tumour arising along the axial skeleton. This entry describes developmental relationships for reference and is not a basis for diagnosis, prevention counselling, or treatment.

Evidence & guidelines

The account here is based on experimental embryology and molecular developmental biology in vertebrate models, beginning with organizer transplantation and extended by the molecular identification of inducing and patterning signals, together with standard human embryology texts rather than clinical guidelines.

History

The capacity of the dorsal organizer to induce a nervous system was demonstrated in the 1924 transplantation experiment of Spemann and Mangold, which showed that grafted organizer tissue could induce a secondary axis with a neural tube in the host. The molecular basis remained obscure until the 1990s, when organizer-secreted BMP antagonists such as noggin and chordin were identified and neural induction was reframed as a default state revealed by BMP inhibition.

Debates

Is neural fate a true 'default' state, or does it require active instruction?

The default model holds that ectoderm becomes neural simply when BMP signalling is blocked, but subsequent work suggested that additional instructive signals (for example FGF) contribute, so the relative roles of inhibition versus active induction remain discussed.

Key figures

• Hans Spemann
• Hilde Mangold
• Ali Hemmati-Brivanlou
• Douglas Melton
• Richard Harland

Seminal works

• spemann-mangold-1923
• smith-1992-noggin
• hemmati-brivanlou-melton-1997

Frequently asked questions

What is neural induction?

It is the process by which signals from the organizer and notochord direct part of the ectoderm to become the neural plate, the precursor of the brain and spinal cord, largely by inhibiting BMP signalling.

What happens to the notochord in the adult?

The notochord is a transient embryonic structure that helps pattern the body axis; most of it regresses, and in the mature spine it persists only as the nucleus pulposus within the intervertebral discs.