Lecture 9 Neural induction and NT patterning

BMP4

TGFβ receptors on adjacent cells

Differentiation into epidermal ectoderm

Gsc and siamois

Intrinsically

chordin, noggin, follistatin

• They diffuse into the same EC spaces and compete effectively for binding to the BMPs so they can no longer activate their receptors

BMP antagonists result in ectoderm cells changing their fate to neural identity in neural induction

BMP antagonists act on the rest of the ‘non-organiser’ mesoderm to refine mesodermal fate

• Low level Nodal gives the ventral mesoderm • High level Nodal gives the organiser • Signals from the organiser acts to inhibit BMPs to dorsalise and pattern adjacent mesoderm • At the same time, antagonism of BMPs –> Gives a neural identity

Ventral mesoderm

organsier

blood then kidneys lowest conc of BMP antagonists

somites and heart

• 1920s Organiser graft experiment, Spemann + Mangold • Grafted an organiser (the bit of induced mesoderm that lies directly above the Nieuwkoop centre) from a donor to a host newt (similar to a Xenopus), and found that a ‘twinned’ embryo developed - with a complete secondary neural axis.

HOST host derived shows that the neural tissue was induced from the ectoderm in response to signalling from the organiser

The axial mesoderm (prechordal mesoderm and notochord) and anterior endoderm was donor derived and therefore differentiates from the organiser

• Induction is an example of a change in fate mediated by extrinsic/non cell-autonomous event • It can be from a signal or lack or signal e.g. lack of BMP  neural

This is different to a change in fate from cell autonomous/cell intrinsic differentiation where there is a different distribution of cytoplasmic determinants, causing the cell to divide asymmetrically. One daughter stays same fate as mother. Second daughter inherits different components and cell-autonomously differentiates to alternate Cell fate X.

The anterior-posterior axis becomes apparent as cells in the organiser autonomously differentiates into the axial mesendoderm This causes the dorsal mesoderm to involutes and undergo convergent extension to lie under the ectodermal layer of the embryo. Convergent extension (gastrulation) causes this change in shape to form a long thin rod of axial mesoderm cells sitting under the ventral midline of the neural tube. As these processes occur, the neural plate grows and elongates along the A-P axis, and rolls into the neural tube.

• Anterior endoderm (AE) • Prechordal mesoderm (PM) • Notochord (NC) mostly

It means that the A end of NP is underlaid by different cell types to P end. Anterior endoderm/prechordal mesoderm induce ‘brain-like’ neural transcription factors e.g. Otx2; notochord induces ‘spinal cord-like’ neural TFs

Activation-transformation model

• It is the basis for formation of forebrain brain (A) versus hindbrain and spinal cord (P)