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Early Development of Neural Tube
Development of Medulla Spinalis and
Peripheral Nervous System
Assoc.Prof. E.Elif Güzel, M.D.
Third week of Embryogenesis
• Primitive streak/pit appears on the epiblast (day 15)
• 3 germ layers differentiate (gastrulation)
– Embryonic ectoderm
– Intraembryonic mesoderm
– Embryonic endoderm
Formation of the Neural Plate
• In the 3rd week, developing notochord and the paraxial mesoderm induces
overlying ectoderm (cranial to the primitive streak) to become neuroectoderm.
• The elongated, slipper-shaped plate of thickened ectoderm is called the neural
plate (day 18).
• Inducing signaling molecules are the members of TGF-β family (Shh and BMPs).
• Neural plate invaginates- neural groove, lateral edges elevates- neural folds (day 20)
Neurulation (Formation of the neural tube)
• Neural groove invaginates and neural folds approach each other and fuse to form
the neural tube (day 22).
• Fusion begins in the cervical region (4-6 somite level) and proceeds in cephalic
and caudal directions.
• Cephalic region -future brain, caudal region -future spinal cord.
• Neural tube detaches from the surface ectoderm which will form the epidermis.
• There are 2 parts where the neural tube is still open and in
communication with the amniotic cavity:
– Cranial neuropore
– Caudal neuropore
• These opened parts will close at
– 25th – 27th day
• As the neural plate invaginates,
ectodermal neural crest cells appear at
the border.
• As the neural tube detaches from the
surface ectoderm neural crest cells fuse,
undergo into mesenchymal transition,
and remain between the surface
ectoderm and the neural tube.
• Neural crest cells migrate through the
periphery and differentiate into many
cell types.
Derivatives of neural tube
• Brain
• Spinal cord
– Neurons and supporting cells of the CNS
– Somatomotor neurons of the PNS
– Presynaptic autonomic neurons of PNS
Derivatives of the neural crest
•
•
•
•
•
•
•
•
Sensory neurons in the PNS
Postsynaptic autonomic neurons
Schwann cells
Arachnoid and piamater of meninges
Odontoblasts
Adrenal medulla cells
Head mesenchyme
Melanocytes in the skin
Development of medulla spinalis
• The neural tube caudal to the 4th pair of somites develops into the spinal
cord.
• The walls of the neural tube thicken.
• Size of the neural canal gradually reduces and persists as central canal at
week 10.
Cytodifferentiation of the neural tube
• The wall of the recently closed neural tube- neuroepithelial cells
(pseudostratified ep.)
• Neuroepithelial cells divide…neuroblasts… form the mantle zone
(around the neuroepithelial layer)
• After neuroblast formation stops, the neuroepithelium gives rise to glioblasts
which migrate to mantle and marginal zones.
• When the neuroepithelial cells cease producing neuroblasts and glioblasts, they
differentiate into ependymal cells.
• Microglial cells are mesenchymal, they invade the CNS in fetal period with the
blood vessels.
• Various stages of development of a neuroblast
• Neural tube is composed of 3 layers;
1. Ventricular (ependymal) layer
–
innermost cells lining the lumen
2. Mantle layer (gray matter)
–
–
the neuroblasts migrated from the
neuroepithelium
future gray matter of the spinal cord
3. Marginal layer
–
–
–
outermost
processes of cells in the mantle zone
future white matter of the spinal cord
• Proliferation and differentiation of neuroepithelial cells in the developing
spinal cord produce thick walls and thin roof-, floor- plate.
• Differential thickening of the lateral walls produces longitudinal groove on
each side- sulcus limitans.
• Alar plate forms the dorsal horn of the gray matter
• Basal plate forms the ventral horn of the gray matter
• Sulcus limitans seperates the alar plate from the basal plate.
• The ventral root of the spinal nerve is composed of nerve fibers arising
from neuroblasts in the basal plate, whereas the dorsal root is formed by
nerve processes arising from neuroblasts in the spinal ganglion.
Development of the spinal ganglia
• Neural crest cells differentiate into
– pseudounipolar neurons
– satellite cells
Development of meninges
• Develop from cells of the neural crest and mesenchyme
(days 20-35)
• Primordial meninges
– External dura mater
– Internal pia arachnoid (leptomeninges)
• Fluid filled spaces occur between leptomeninges and form the
subarachnoid space
• Leptomeninges subdivides into pia mater and arachnoid mater
Positional changes of spinal cord (SC)
•
•
•
•
•
Firstly, SC extends the entire length of the vertebral canal and spinal nerves (SN) pass
through the intervertebral foramina at the levels of their origin.
Vertebral column (VC) and dura mater grow more rapidly than the SC, the caudal end of
the SC gradually comes to lie at relatively higher levels.
The SN run obliquely from the SC to the corresponding level of the VC.
In adults SC ends; L2-L3, dura- and arachnoid-mater end; S2.
Pia mater, passes through the dura and attaches to the periosteum of the 1st coccygeal
vertebra (filum terminale) (indicates the original level of the end of spinal cord).
Myelination of nerve fibers
• Myelin sheaths begin to form during the late fetal period and continue
to form during the first postnatal year.
• Oligodendrocytes originate from neuroepithelium.
• Schwann cells originate from neural crest cells.
Development of PNS
• All sensory cells of PNS (e.g. dorsal root ganglia, trigeminal ganglia)
are derived from neural crest cells.
– Peripheral sensory cells are at first bipolar, then they differentiate into unipolar
cells (except the sensory cells in the ganglion of CN VIII)
• Multipolar cells in the autonomic ganglia derives from neural crest
cells.
• Satellite cells derives from neural crest cells.
• The connective tissue around the ganglion cells are derived from
mesenchyme.
Development of spinal nerves
• As the limb buds grow, the axons from spinal cord segments (multipolar
neurons derived from basal plate) elongate and grow into the limb (end of
4th week).
• Sensory neurons give extensions to form spinal nerves as well.
• Connective tissue sheaths of the peripheral nerves are derived from
mesenchyme.
References
1.
2.
3.
4.
The Developing Human: Clinically Oriented Embryology by Keith L.
Moore, T. V. N. Persaud and Mark G. Torchia (2013). 9th ed. Elsevier
Saunders, Philadelphia. ISBN: 978-0-8089-2444-9
Langman’s Medical Embryology by T.W. Sadler (2012). 12th ed.
Lippincott Williams & Wilkins, Philadelphia. ISBN: 978-1-4511-4461-1
Human Embryology by Larsen WJ (2001). 3rd ed. Churchill
Livingstone, Philadelphia. ISBN: 978-0-443-06583-5
Netter’s Atlas of Human Embryology by Larry R. Cochard (2002). 1st
ed. Icon Learning Systems, New Jersey. ISBN: 0-914168-99-1