Nervous System Development

Nervous System Development

1. Somites

   • Myotome (epimere)
   • Myotome (hypomere)
   • Scelerotome
     • Vertebral
       • 7 cervical, 12 thoracic, 5 lumbar, 3 sacral
   • Dermatome

2. Neural tube (spinal chord)

   • cervical c0-c6, thoracic c6-t9, lumbar T9-T11, sacral T11-L2
   • Dorsal Horn: somatic (pain, temp, touch) and autonomic (sympathetic, parasympathetic)
   • Ventral Horn: motor somatic and autonomic

3. neural crest (glia) become all peripheral nerve and somatic sensory ganglia differentiate into: melanocytes, dorsal root ganglia, autonomic ganglia, chromaffin cells of adrenal medulla, preaortic ganglia, enteric (gut) ganglia)

   • spinal nerve for every vertebrae level each with corresponding dermatome and myomtome
     • Spinal nerve levels C5-T1
       • C6 above C6
         • Dermatome level thumb
         • Mytome level Flex bicep. Reflex, hit lateral side of wrist
       • T1 below T1
         • Dermatome level medial eblow
         • Myotome level pinkie to thumb, spread/close fingers
       • C5 Located above C5
         • Dermatome level lateral shoulder
         • Myotome level Deltoid (adduction of gelnialhumoral joint. Reflex hit lateral elbow
       • C7 above C7
         • Dermatome Level middle finger
         • Myotome level extension of triceps, wrist fingers. Reflex, hit elbow bone
       • C8 below C7
         • Dermatome level pinkie finger
         • Myotome level flexion of wrist up and down
     • Spinal nerve levels L2 to S1
       • L2 below L2
         • Dermatome Lateral Thigh (Inguinal??)
         • myotome flex hip joint
       • L3 below L3
         • Dermatome level medial thigh above knee
         • myotome level adduct hip joint
       • L4 below L4
         • dermatome level medial malleolus
         • knee extension, knee reflex
       • S1 below S1 pedicle
         • lateral calcaneal
         • plantar flexion, reflex strike against achilles tendon
   • Paravertebral Ganglia: form sympathetic chain, pre ganglionic sympathetic neuron (in front of notochord)
     • Sympathetic nervous system (fight or flight) originates in lateral horn, exits through ventral root, through spinal nerve trunk, enters sympathetic chain through white ramus communicons, moves through chain to desired spinal level, synapses, exits grey ramus communicons (now post ganglionic), travels to desired organ
   • Pre-aortic ganglia (in front of aorta or prevertebral ganglia): post ganglionic sympathetic neurons
   • (Sensory) Dorsal root ganglia: neural crest cells don't migrate, extend peripheral axons to dermatome, central pathways into Dorsal horn gray matter
     • Dorsal root (one way) merges with spinal nerve trunk (two way) which breaks into the dorsal and ventral ramus, dorsal innervates epaxial back muscles, ventral innervates body wall and limb muscles
   • Intramural ganglia (migrate into viscera): collection of cell bodies inside the organ, post ganglionic parasympathetic neurons
     • Parasympathetic (rest and digest), originates in lateral horn pre ganglionic much longer, doesn't synapse with post ganglionic until at the desired organ. Neurons originate from brainstem and S2,S3,S4.
   • Join with ectodermal placodes (thickening of cells under ectoderm) to form all sensory ganglia of head/cranial nerves)

4. Signals from notocord signal formation of Neural plate, involuting to become the neural tube

   • Ectoderm originally secretes BMP4, a signaling molecule that binds to receptors in ectoderm that prevents neural plate formation
     • at gastrulation, the notocord secretes chordin, follistatin and noggin (C/F/N) . All BMP4 binding proteins that locally inactivate BMP4, ectoderm forms neural plate
       • caudal and cranial opening of neural tube are neuropores
   • Neural tube defects (up to 70% can be prevented by maternal use of Folic acid prior to and during pregnacy)
     • Spinal bifida: neural tube fails to close,
       • occulata: layer of skin covers opening in vertebrae, no pertrusion of neural tissue
       • meningocele: CSF and meninges pertrude through abnormal space in vertebrae (not spinal cord)
       • Meningomyelocele: spinal cord and neural elements pertrude through opening of vertebrae
       • Rachischisis: neural tube folds incorrectly, ending up on the outside of vertebrae
     • Anencephaly- upper part of neural tube doesn't close all the way, leaving baby with part of brain and skull missing
     • Axis Development (paracrine signaling)
       • Cranial-Caudal, thought to be infulenced by Hox genes which are organized in a cranial caudal pattern the same as organized on chromosome, pattern similar in many organisms
       • Dorsal-Ventral (roof and floor plate- aneural structures)
         • Roof plate of neural plate secrete BMPs and WNTs which induce formation of dorsal progenitors and dorsal neurons at different concentrations, also inhibits formation of ventral progenitors
           • BMP 3 roles- inhibit neural plate formation, dorsal development, directing migration of meural crets cells
         • floor plate secretes sonic hedge hog (SHH) which induces formation of ventral progenitors and ventral neurons at different cocentrations, also inhibits formation of dorsal progenitors

5. Organization of CNS

   • At 4 weeks formation of 3 primary vesicles superior to spinal cord, 5 weeks formation of 5 vessicles
     • Forebrain (prosencephalon)
       • Telencelphalon
       • Diencephalon
         • thalamus and hypothalamus
         • evagination of central nervous tissue forms eyes, lens formation induced from formation of placode from overlying ectoderm, lens rolls up into body, leaving lense covered by cornea with CNS behind it
     • midbrain
       • Mesenchephalon
     • hindbrain (rhombencephalon)
       • Metenchephalon (pons and cerebrellum)
       • Myelencephalon (medulla)
     • Formation of Felxures (folding)
       • 1st- mesencephalic flexure (at midbrain level)
       • 2nd- cervical flexure (between hindbrain and spinal cord), eyes facing down
       • 3rd- pontine flexure folds the opposite direction into the metencephalon, bringing hindbrain back up. Induces formation of Cerebellum
       • 4 ventricles, all from original lumen of neural tube
         • Lateral Ventricles (cerebral hemispheres)
         • Cerebral aqueduct (through midbrain)
         • Third ventricle (bound by thalamus and hypothalamus)
         • 4th ventricle (level of pons and medulla)
         • 6 layers of Cortex) Inside out development
           • stem cells adjacent to lumen, produce cells that migrate up radial glial cells towards meniges. Oldest cells form deepest layer of cortex
           • formation on gyri and sulci to allow for more surface area for more neurons to develop
           • Defects in cell migration
             • lissencephaly (smooth/glass like brain)
               • initiation defect- cells don't migrate, stay in lumen
               • ongoing migration defect- cells don't know when to stop
               • lamination defect- cells in layers, but layers are disrupted
               • stop signal defect, cells migrate beyond top layer, outside the brain
   • organization of neural tube and spinal cord
     • neuroblasts and neural tube organize into alar (dorsal) and basal (ventral) columns
       • Neuroepithelial cells make alar (sensory) and basal (motor) plates derived from signals from the roof and floor plate
         • Medulla
           • sensory neurons migrate ventrally to give rise to Olivary nuclei
         • Pons
           • sensory neurons migrate ventrally to give rise to Pontine nuclei
         • mesencephalon
           • sensory neurons migrate ventrally to become substantia nigra