Development of Nervous System

Question 1

Neurulation

Answer 1

Form notochord + prechordal mesoderm
Neural induction: overlying ectoderm thickens neural plate (correspond to underlying notochord), cells of plate = neuroectoderm
Lengthen neural plate + body axis - convergent extension (lateral to medial movement cells in plane of ectoderm and mesoderm, regulate by signalling through planar cell polarity pathway, essential for neural tube development)
Neural plate lengthens, invaginate, lateral edges elevate = neural folds
Depressed mid-region = neural groove
Neural folds approach each other in midline, fuse (begin in cervical region, proceed cranially and caudally)
Neural tube form
Before fusion complete, cephalic and caudal ends communicate w/ amniotic cavity (via neuropores)
Result: closed tubular structure w/ narrow caudal portion (spinal cord) and broad cephalic portion (brain vesicles)

Question 2

Neural tube defects

Answer 2

Neural tube closure fails
Cranial region: most of brain fail to form = anencephaly
Cervical region caudally = spina bifida

Question 3

Neural crest cells (NCC)

Answer 3

Cells at lateral border between neural tube and overlying surface ectoderm
Fundamental for formation of many organs and tissues

Question 4

Neural crest cells - epithelial to mesenchymal transition

Answer 4

As neural folds elevate + fuse, NCC start dissociating
NCC undergo epithelial to mesenchymal transition - leave neuroectoderm by active migration/ displacement, enter underlying mesoderm

Question 5

NCC - trunk region

Answer 5

Leave after neural tube closed
Migrate along 1 of 2 paths:
(1) Dorsal pathway - through dermis, enter ectoderm through holes in basal lamina, form melanocytes in skin/hair follicles
(2) Ventral pathway - through anterior half of somites, become sensory/dorsal root/autonomic ganglia, sympathetic/enteric (gastrointestinal tract) neurons, Schwaan cells, cells of adrenal medulla

Question 6

NCC - cranial neural fold region

Answer 6

Leave tube before closure

Form: craniofacial skeleton, cranial ganglia, glial cells, melanocytes

Question 7

Planar cell polarity pathway

Answer 7

First discovered in drosophila
Breaks cellular symmetry - converts tissue gradients (signalling molecules) to sub cellular asymmetry
Amplifies sub cellular asymmetry Communicates polarity between cells

Question 8

Molecular regulation of neurulation - induction of neural plate

Answer 8

Upregulate FBF:
Promote neural pathway, Repress bone morphogenetic protein (BMP) 4 transcription, Upregulate express CHORDIN, FOLLISTATIN and NOGGIN (inhibit BMP activity) present in organiser (primitive node), notochord, prechordal mesoderm

Question 9

Molecular regulation of neurulation - BMP4

Answer 9

Induce ectoderm to form epidermis
Induce mesoderm to form intermediate + later plate
No exposure to BMP4 = ectoderm ‘default state’ - NEURAL TISSUE (forebrain + midbrain only)

Question 10

Molecular regulation of neurulation - axis patterning

Answer 10

WNT3a + FGF = induce caudal neural plate structures

Retinoic acid = organise cranial-caudal axis, regulate express homeobox genes

Question 11

Segmental pattern of somatic motor + sensory innervation (PNS)

Answer 11

Pattern established by segmental organisation of somites
Intercostal muscles innervated by spinal nerve at same level
Skin: each dermatome innervated by spinal nerve at same level (some overlap)