12 - The Ectoderm 

Germ layer derivatives 

Includes: 

• Neural crest (eg. pigment cells)

• CNS 

• Outer surface (epithelial)

Neurulation 

• Production of the central nervous system 

• Different regions arise 

• Folding occurs within a relatively short period of time 

• Adhesion between cells in the neuroepithelium us maintained by N-cadherin expression; neural crest cells must lose this in order to migrate 

• Neural crest cells don't have any N-cadherin in order to become migratory so this differentiates the neural crest cells from the neural epithelial cells 

• Notochord and the floor plate are important signalling centres 

Neural crest fates 

• Neural crest cells will give rise to the peripheral nervous system, Schwann cells (insulating glial cells of the CNS) and melanocytes 

sox10-lacZ neural crest marker visualised 

Cranial neural crest 

• A number of discernible NC streams occur during head development 

• These form the frontonasal process (FNP) and the pharyngeal arches (PA1, PA2)

• Somites help in the identification of different regions 

Early brain development 

• Rostral part is what gives rise to the brain 

(Slightly) later brain development 

• Large changes over time 

• Massive growth - especially of the forebrain 

• Midbrain and hindbrain stay relatively small in comparison

The (chick) brain 

The ‘typical’ vertebrate brain 

Evolutionary developmental biology 

• Brain has extremely complex evolutionary history - especially in human lineage

• Changing patterns of neural progenitor behaviour can lead to drastic alterations in adult neuroanatomy 

• Some brain regions have evolved to contain huge numbers of neurons via increase in progenitor proliferation 

• These regions are folded 

• Folded cerebella are found in all mammals and bird 

• Folded cortices are found in many mammalian groups 

Signalling and patterning 

• The brain is ‘patterned’ by signalling centres and transcription factors 

ANR = anterior neural ridge 

MHB = midbrain-hindbrain boundary 

ZLI = zona limitans intrathalamica 

Chick brain: 

Drosophila 

• Developmental model organism 

Wildtype: 

Ultrabithorax: 

(mutant) 

2x wings and 2x thoracic segment 

Hox genes

• Code for transcription factors 

• Identify anterior / posterior 

• Homeotic phenotypes were catalogued in the 1970s

• Homeotic genes are responsible for the Hox genes 

• Hox genes are members of the homeobox superfamily of transcription factors - found in clusters in the genome 

Homeobox genes 

• Homeobox encodes the homeodomain 

• Homeodomain binds to DNA (transcriptional regulation) 

• The ‘box’ is the part of the protein that binds 

• Oxt2 and Gbx2 are other homeobox transcriptional factor genes 

Hox patterning in the hindbrain 

• There are 4 paralogous (ie. evolutionary sister) Hox clusters in mammals 

• Their expression controls the identity of hindbrain segments on the AP axis (in an anterior-posterior pattern)  

The chick - as a development

• Similarities to mouse development but can be manipulated inside the egg

1. At desired developmental stage, the egg is ‘windowed’ and embryo is visualised 

2. Injection of vectors into the chick using electrodes and current 

3. After manipulation, the ‘window’ in the chick egg can be tapes shut and the embryo continues developing 

• Injection of green fluorescent vector into the developing brain ventricles 

• Only in one side - we can manipulate one side while the other side remains unchanged as a control 

• Hoxb1 respecifies trigeminal motor axons to a facial identity 

• Normally, Hoxb1 wouldn't be expressed by if you inject a vector with GFP - you can get the expression into the pharyngeal arches 

Dorsoventral patterning

BMPs/Wnts - signalling molecules that are expressed on the dorsal side 

Shh - expressed on the ventral side (floor plate and notochord)

There is dorsoventral (including NC) organisation to the spinal cord: 

• Primary sensory neurons (mostly posterior dorsal side) 

• Commissural interneurons 

• Motor neurons (ventral region)

Signalling pathways in dorsoventral patterning 

• Patterning of the proliferative progenitor cells in the neuroepithelium: 11 domains of neural progenitor cells - 5 ventral and 6 dorsal (left picture) - each with a specific combinatorial code of transcription factors 

• Cells migrating to the marginal layer from these domains of neuroblasts (right picture), six groups of sensory-related interneurons dorsally and four groups of motor-related interneurons ventrally plus the motor neuron group (MN) 

• Shh is secreted by the notochord and floor plate

• Wnts and Bmps are secreted by the roof plate and surface ectoderm

• Retinoic acid (RA) is secreted by adjacent somites  

Transcription factor codes 

• Many transcription factors from the homeobox family specify the dorsoventral pattern 

• Transcription factors of the basic Helix-loop-helix family - induce neurogenesis (process of neuron production from proliferative neural-progenitor cells in the neuroepithelium 

• Some transcription (some homeobox) act to drive postmitotic differentiation 

Cortex development 

• Glutamatergic projection neurons are born locally - then they follow an inside out pattern as they migrate radially from the ventricular zone to the cortical plate 

• GABAergic interneurons are born in the ganglionic eminences (LGE, MGE, CGE) - they undergo tangential migration into the neocortex

Corticogenesis 

• Cortical neurogenesis proceeds in an inside out pattern 

Mammalian neocortex 

• Has 6 layers 

• Born in an ;inside out’ pattern 

• Composed of glutamatergic projection neurons and inhibitory GABAergic interneurons that migrate in from the ventral forebrain 

(Cortical) neural progenitors over time 

Radial glia 

• Acts as scaffolds during development 

• They span the apical-basal axis 

• They are also the progenitor cells 

• The signalling molecule reelin is secreted from glial endfeet 

The microtubule binding protein double cortex is expressed by migrating neurons: 

Normal mouse cortex 

In the mutant (reeler) 

• Reelin is not expressed or not expressed in the usual way