Lecture 9: vertebrate development II Flashcards
Describe gastrulation.
The three germ layers start to become different tissues.
Early gastrula = dorsal lip tissue migrates over blastocoel roof
Mid gastrula = early dorsal lip tissue moved deep into the interior of the embryo. Becomes pharyngeal endoderm and prechordal mesoderm.
At dorsal blastopore lip = becomes posterior end of the notochord.
Describe the result of Organiser in gastrulation.
EARLY or MID-GASTRULA stage Organizer gives rise to pharyngeal endoderm and prechordal mesoderm - inhibit both Wnt and BMP signalling on the dorsal side => head and brain tissue induced.
LATE GASTRULA stage Organizer made of notochord precursors only will ONLY inhibit BMP signalling => trunk and spinal cord induced.
This has profound consequences for the CHARACTER of the second axis that an EARLY or LATE Organizer can induce.
By inhibiting BMP signalling (noggin and chordin from organiser) in the ectoderm, neural fate is realised BECAUSE epidermal fate is suppressed, i.e., in a real sense, NEURAL fate is the default fate of embryonic ectoderm, and BMP is an inducer of EPIDERMAL fate.
Wnt antagonists from the organiser induce anterior character within neural tissue, promoting brain development by antagonising the Wnt signals in the mesoderm.
Explain the two gradient model of embryonic axis formation.
1 - An A-P gradient of Wnt signalling activity in the developing neural plate, which is lowest in the anterior (where Wnt antagonism is highest from Pharyngeal Endoderm and Prechordal Mesoderm)
2 - A D-V gradient of BMP signalling activity, that is lowest in the neural plate and the dorsal axial mesoderm, (where BMP antagonist activity is highest from noggin in Prechordal Mesoderm and Notochord).
So, dual inhibition of Wnt and BMP signalling in the anterior neural plate promotes brain formation, and sustained BMP inhibition without Wnt inhibition promotes spinal cord formation.
In the Early Gastrula, prechordal mesoderm and pharyngeal endoderm first signal to the anterior neural plate, which then activates Anterior TFs that specify brain tissue.
Notochord represses Anterior TF in the mid-gastrula stage.
By the late-gastrula stage notochord has activated further posterior TFs in the spinal cord.
Describe neural tube formation and establishment of the A-P axis.
Activation-Transformation Model to explain A-P neural tube patterning.
In the Activation Step, the Organizer secretes Wnt and BMP inhibitors which promotes forebrain fate in the neural anterior character.
In the Transformation Step, secretion of Wnt antagonists by the Organizer is lost, and the posterior neural plate is exposed to (as well as BMP antagonists) multiple gradients of posteriorizing factors, such as some Wnts, Retinoic Acid and FGFs. Forebrain fate is suppressed and over time, increasingly posteriorized fates are adopted by neural plate cells.
Summary:
Anterior-Posterior regionalization of the neural tube is achieved by two opposing gradients: antagonistic signals of Wnt and BMP promoting anteriorisation and neuralization; and Wnt, FGF and Retinoic Acid promoting posteriorisation.
These introduce complex patterns of differential gene expression across the AP axis, allowing regionalization of the CNS.
Distinct domains of the vertebrate spinal cord and vertebral column are defined by specific combinations of Hox TFs, which can be modulated by exposure to exogenous posteriorising factors such as Retinoic Acid.
Similarly, in the brain, subdivision into forebrain, mid-brain and hindbrain is regulated by posteriorizing factors such as Wnt, RA and FGFs.
Explain the establishment of relative D-V territories within a defined tissue (neural tube).
The neural plate is induced initially as a single cell thick epithelial sheet, defined at its periphery by a group of cells called the Dorso-Lateral-Hinge Point (DLHP) cells, that will eventually delaminate from the neurectoderm as neural crest cells, separating the closed neural tube from overlying epidermis.
The neural tube is polarised along its D-V axis by two opposing signalling systems:
1 – TGFbeta ligands secreted by the dorsal roof plate – induce dorsal neuronal fates.
2 – SHH secreted by the ventral floor plate – induce ventral neuronal fates by regulating Pax genes.
3 – also Wnt signals secreted by the floor plate to promote expression of BMPs in roof plate and contribute to expression of the neural crest cells.
The TF expressed define distinct neural identities that are realised when progenitors terminally differentiate into specific neuronal subtypes a few days later.
How do BMP antagonists govern neural induction and dorsalisation of mesoderm?
- Inhibition of BMP signalling in the ectoderm prevents epidermal fate being adopted and enables ectoderm cells to pursue the default neural fate
- inhibition of BMP in the mesoderm prevents ventral mesodermal fates from being realised and enables notochord and somite fate to be adopted instead
Prechordal mesoderm and notochord are derivatives of axial mesoderm. Explain how Shh and TGF-B proteins create D-V patterns in the neural tube.
- Shh is a morphogen secreted by notochord and floor plate, ventrally located midline structures. It acts on neighbouring cells in the overlying neural tube in a concentration dependent manner to induce distinct neuronal cell fates within the ventral spinal cord.
- A small number of TGF-B related proteins including BMP4, 5 and 7 are produced dorsally. They act in partially overlapping domains in the dorsal neural tube to induce a range of neuronal cell fates.
- Opposing Shh and TGF-B gradients polarise the D-V axis by inducing the transcription of genes encoding specific TFs.
