Development of Brain Stem, Cerebellum and Cerebrum

• The neural tube cranial to the 4th pair of somites develop into the brain.

• 3 dilatations and 2 flexures form at the cephalic end of the neural tube during the 4th week.

flexures: 1) Cephalic flexure (midbrain region) 2) Cervical flexure (hindbrain-SC)

primary brain vesicles 1) Prosencephalon (forebrain) 2) Mesencephalon (midbrain) 3) Rhombencephalon (hindbrain)

• Secondary brain vesicles (5th week) and their derivatives…

Brain flexures • Midbrain flexure-Cervical flexure. • Unequal growth of the brain between flexures produces

the pontine flexure in the opposite direction (5th week). This flexure results in thinning of the roof of the hindbrain.

• Initially, the primordial brain has the same basic structure as the developing spinal cord….

• However, the brain flexures produce variations in the position of white and gray matter.

Hindbrain

• Spinal cord-servical flexure-hindbrain

Myelencephalon

• The caudal part of the myelencephalon (future closed part of medulla) resembles the spinal cord.

• Central canal • Neuroblasts from the alar plates migrate into the marginal zone-

nucleus gracilis, nucleus cuneatus • Pyramids

• The rostral part of the myelencephalon (future open part of medulla) is wide and rather flat.

• Roof plate is streched and thinned. • Neural canal (future 4th ventricle) becomes rhomboidal-diamond shape. • As the alar plates come to lie lateral, the sensory nuclei develop lateral to

the motor nuclei. • Neuroblasts in the basal plates develop into motor nuclei. • Neuroblasts in the alar plates develop into sensory nuclei.

Metencephalon

• Walls form the pons and cerebellum.

• Cavity forms the superior part of the 4th ventricle.

• Develops from thickenings of dorsal parts of the alar plates (cerebellar swellings).

• The swellings enlarge and fuse in the median plane, cerebellar vermis and hemispheres forms.

• Pontine flexure causes divergence of the lateral walls. • Neuroblasts of each basal plate develop into motor nuclei. • Some neuroblasts from the alar plate….pontine nuclei

Cerebellum

Pons

• The primary fissure forms and divides the cerebellum into anterior and middle lobes.

• Continued fissuration subdivides the expanding cerebellum into further lobes and then, starting in the 3rd month, into lobules and folia.

• The structure of cerebellum reflects its evolutionary development; 1. Archicerebellum (flocculonodular lobe) 2. Paleocerebellum (anterior lobe and vermis) 3. Neocerebellum (posterior lobe)

• Neuroblasts of the mantle zone of the alar plate migrate to the marginal zone, differentiate into the neurons of the cerebellar cortex.

• Other neuroblasts of the alar plates give rise to central nuclei (e.g. dentate nucleus)

Choroid plexuses

• Thin ependymal roof is covered by piamater with numerous blood vessels. This vascular membrane together with the ependymal cells forms the tela choroidea of the 4th ventricle.

• Pia mater proliferates and tela choroidea invaginates the 4th ventricle and differentiates into choroid plexus.

• Similar plexuses develop in the roof of the third ventricle and the medial walls of the lateral ventricles.

Midbrain

• Neural canal….. Cerebral aquaduct • Neuroblast from the alar plates migrate to form sup/inf colliculi at tectum. • Neuroblast from the basal plates give rise to groups of neurons in tegmentum. • Substantia nigra; gray matter • Fibers growing from the cerebrum form the crus cerebri.

• Rostral part- telencephalon- primordia of the cerebral hemispheres • Caudal part- diencephalon

Forebrain

• Alar and basal plates and sulcus limitans are recognizable until the junction of midbrain and forebrain!!!

Diencephalon • In the lateral walls of the 3rd ventricle 3 swellings develop

– Epithalamus – Thalamus – Hypothalamus

• Epithalamus- pineal gland

• The growing thalami meet across the third ventricle, form the interthalamic adhesion.

• Hypothalamus

Pituitary gland

• Consists of a median part and 2 lateral cerebral vesicles.

• The lateral ventricle in each hemisphere communicates with the third

ventricle through an interventricular foramen (of Monro).

Telencephalon

• Developing cerebral hemispheres expand in all directions until they

cover the diencephalon.

• The rostral wall of the forebrain, the lamina terminalis, is very thin.

• The mesenchyme trapped in the longitudinal fissure between the cerebral hemispheres; falx cerebri

• The corpus striatum apppears during the 6th week as a swelling in the future temporal lobe.

• The floor of each hemisphere expands slowly than the lateral walls; cerebral hemispheres become C-shaped.

• Corpus striatum divides into the caudate and lentiform nuclei

by the internal capsule (fiber pathway).

• Caudal end of each hemisphere turns ventrally and then rostrally

forming the temporal lobe; it carries the lateral ventricle.

• The expansions of the neural canal in the brain vesicles and cerebral

hemispheres give rise to the cerebral ventricles. • lateral ventricles in the cerebral hemispheres, the

• 3rd ventricle in the diencephalon,

• the narrow cerebral aqueduct (of Sylvius) in the mesencephalon

• 4th ventricle in the rhombencephalon.

• The telencephalon gives rise to commissural tracts that connect corresponding areas of the left and right cerebral hemispheres. These include the anterior and hippocampal commissures and the corpus callosum.

• The small posterior and habenular commissures arise from the epithalamus.

• Initially the surface of the cerebral hemispheres is smooth

• As growth proceeds sulci and gyri develop

• The walls of the developing cerebral hemispheres initially show the 3 typical zones of the neural tube (ventricular, mantle, marginal).

• Cells of the mantle zone migrate to the marginal zone and give rise to the cortical layers.

• Morphogens and transcription factors play role in the development of nervous system.

• Dorsal to ventral gradient of sonic hedgehog (Shh) and bone morphogenetic proteins (BMPs) determine dorsal-ventral cell fates.

• Shh ventralizes the neural tube, induces the floor and basal plates. • BMPs increase the expression of dorsalizing genes; PAX3, 7 in the

alar and roof plates.

References

1. 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

2. Langman’s Medical Embryology by T.W. Sadler (2012). 12th ed. Lippincott Williams & Wilkins, Philadelphia. ISBN: 978-1-4511-4461-1

3. Human Embryology by Larsen WJ (2001). 3rd ed. Churchill Livingstone, Philadelphia. ISBN: 978-0-443-06583-5

4. Netter’s Atlas of Human Embryology by Larry R. Cochard (2002). 1st ed. Icon Learning Systems, New Jersey. ISBN: 0-914168-99-1

5. Human Embryology and Developmental Biology by Bruce M. Carlson (2009). 4th ed. Mosby, Elsevier, Philadelphia. ISBN: 978-0-323-05385-3