Neurulation & Development of the PNS Flashcards
___ incudes neuroectoderm to form Neural Plate
Notochord
What week does Neurulation begin?
Beginning of week 3
What makes up the ectoderm during neurulation?
- Neuroectoderm
- Surface Ectoderm
__-__ spine formation occurs during Primary Neurulation
Cervical-Lumbar (coccygeal and sacral regions undergo secondary neurulation)
What day does the neural plate form?
Day 17
During Primary Neurulation, the Notochordal Plate is __ to the Notochord, which is ___ to the Neural Plate
- Inferior/below
- Inferior/below
Need ___ in order to close the rostral & caudal neuropore
Folate
What signifies the end of Primary Neurulation?
Closure of the caudal neuropore at somite 31 (NT extends past this caudally into sacral and coccygeal regions)
What day does the Caudal Neuropore close?
Day 26
What day does the Rostral Neuropore close?
Day 24
What develops from the tail bud?
- Caudal-most NT
- Neural crest cells
- Somites
Secondary Neurulation
- Formation of the neural tube from the tail bud
- Involves the making of a medullary cord and its subsequent hollowing into a neural tube
- Closing of caudal neuropore is merged with the forming tail bud
Medullary cord grows ___ to primitive streak
Inferior
Steps of Secondary Neurulation
(1) Tail bud condenses into a solid mass, the medullary cord
(2) Medullary cord develops a lumen
(3) Lumen of medullary cord becomes continuous with more cranial neural canal – merges with central canal or neural tube (consists of mixed cells of mesodermal and ectodermal origin)
What days does Secondary Neurulation occur?
Days 20-40
Neural Crest Cells
- Neuroectodermal cells positioned along dorsal neural folds; present bilaterally along entire cranial-caudal NT
Neural Crest cells undergo ___
EMT
EMT
- Epithelial-mesenchymal-transition
- Lose contacts and become migratory
- Migrate ventrally along length of embryo
__ Neural Crest contributes to septation of the heart
Cardiac
Neural Crest Derivatives
- Melanocytes
- Odontoblasts
- Schwann cells
- Spinal & Autonomic ganglia
- Enteric nervous system
- Suprarenal (adrenal) medulla
- Characteristic facial features
- Pharyngeal arch (Malleus, Incus, Stapes, Styloid process, facial bones, Meckels cartilage, Hyoid cartilage, Laryngeal cartilage, Trachael rings)
What are the derivatives of Cardial Neural Crest cells?
- Aortic arch arteries
- Aorta
- Aortic-pulmonary septum
- Pulmonary artery
- Outflow tract
- Pharyngeal arches
- Right and left dorsal aortas
What are 5 Neurocristopathies?
- Goldenhar Syndrome (hemifacial macrosomia)
- Micrognathia
- TCS (Mandubulofacial Dystosis)
- Hirschsprung Disease
- Piebaldism
Goldenhar Syndrome (hemifacial macrosomia)
- Jaw and cheekbones on one side of the body are underdeveloped
- Associated with eye and ear abnormalities, sometimes cleft lip
Micrognathia
Lower jaw is underdeveloped or completely absent
TCS (Mandibulofacial Dystosis)
- Autosomal dominant disorder of craniofacial development
- Often affects jaw, cheekbones, ears, and ears
- Characteristics: downward slanting eyes, very small chin and jaw, hearing loss, and vision loss
Hirschsprung Disease
- Enteric nervous system doesn’t develop
Piebaldism
- Autosomal dominant disorder
- Characterized by the congenital absence of melanocytes in affected areas of the skin and hair
- Affected individuals present at birth with a white forelock and relative stable, persistent depigmentation of the skin with a characteristic distribution
- Due to mutations of the KIT proto oncogene that encodes a tyrosine kinase that is important in nearl crest cells; mutated KIT affects differentiation and migration of melanoblasts from the neural crest
Meningomyelocele
- NTD that can occur anywhere along the vertebral column, but most common in lumbar and sacral region
- involved a malformation of the vertebral arch, meninges, and nervous tissue, covered in a membraneous sac
- Does not lead to immediate death
Cranial Neural Tube Defects
- Typically found in the cervical region of the vertebral column
- May lead to immediate death of the fetus
Why is melanoma so deadly?
It reactivates cell’s migratory genes
What are the meninges?
- Membranes covering the spinal cord and brain
What do the meninges develop from?
- Neural Crest Cells
- Mesenchyme
What day(s) do the meninges develop?
Days 20-35 (3 to 4 weeks)
How is the Meninx Primitiva formed?
- When NCC and mesenchyme migrate and surround NT
- Results in formation of the primordial meninges
What 2 things does the Primitive Meninx differentiate into (days 34-48)?
- Ectomeninx
- Endomeninx
Ectomeninx between 45-60 days:
(1) Ectomeninx becomes more compact and forms spaces for future venous sinuses (collect blood from brain to drain out)
(2) Endomeninx becomes more reticulated and subarachnoid space/cisterns appear
What does the spinal ectomeninx give rise to after it dissociates from the vertebral bodies?
Spinal epidural space – necessary for epidurals
Ectomeninx is the future:
Dura
Endomeninx is the future:
Arachnoid and Pia
Dermal Sinus Tract
- Forms during Primitive Meninx differentiation
- Abnormal tract connecting the epithelium and the spinal neural structures and containing epithelial and/or neural elements
Neural Tube Closure
- Does not occur simultaneously along the length of the NT
- Closure starts in middle of embryo
- Cranial regions are more advanced than caudal regions
- Initiated at several locations along the AP axis
- Results in formation of the cranial and caudal neuropores
During NT closure why are the cranial regions so advanced compared to the rest?
Because the cells are growing faster than they can close causing cranial and caudal neuropores that are closed last (zipped from middle to cranial, and middle to caudal)
How many closure sites are there in NT closure?
5
Failure of any of the NT closure sites results in:
NTDs (cranial and/or spinal)
What factors impact the development of NTDs?
- Genetic
- Nutritional
- Environmental
4,000 pregnancies per year affected by:
NTDs
Encephalocele
- Protrusion of brain tissue (in which the NT is closed) through an opening in the skull
Craniorachischisis (Anencephaly)
- NT is open onto surface of the neck and back
- Occurs at Closure Site 1
- Non-viable
300,000 infants are born with this worldwide each year:
Spina Bifida Aperta
What are the 4 types of Spina Bifida?
- Spina Bifida Occulta
- Spina Bifida Occulta Meningocele
- Spina Bifida Occulta Meningomyelocele
- Spina Bifida Aperta Myeloschisis
Spina Bifida Occulta
- Failure of the posterior vertebral arch to close
- Often tuft of hair present over site where vertebral arch did not close
- Skin is closed
Spina Bifida Occulta Meningocele
- Protrusion of Dura Mater, Arachnoid Mater and CSF but no spinal cord protrusion
- Skin is closed
Spina Bifida Occulta Meningomyelocele
- Protrusion of Dura Mater, Arachnoid Mater, CSF and spinal cord
- Skin is closed
Spina Bifida Aperta Myeloschisis
- Protrusion of Dura Mater, Arachnoid Mater, CSF and spinal cord
- Skin is OPEN
Divisions of CNS
- Brain, eyes, and spinal cord
- Derivatives form from NEURAL TUBE
Divisions of PNS
- Cranial nerves and ganglia
- Spinal nerves and ganglia
- Autonomic nerves and ganglia
- Enteric NS
What does the PNS develop from?
- Neural Crest Cells
- Neuroectoderm
- Ectodermal Placodes
What two regions does the NT divide into?
- Ventral
- Dorsal
What separates the Dorsal and Ventral regions of the NT?
Sulcus Limitans
What is present at the uppermost part of the NT?
Roof Plate
What is present at the lowest part of the NT?
Floor Plate
Alar plate forms from what region of the NT?
Dorsal Region
Basal plate forms from what region of the NT?
Ventral
Alar plate extends __ and __ from the NT
Dorsally and Laterally
Basal Plate extends __ and __ from the NT
Ventrally and Laterally
What is the NT comprised of?
Germinal Neuroepithelium
Neural crest cells migrate from which embryonic structure?
Neural Folds
What are the 3 areas of Neural Tube differentiation?
- Ventricular Zone
- Mantle/Intermediate Zone
- Marginal Zone
Ventricular Zone
- Stem cells positioned closest to lumen
- Will divide and migrate
- cells typically -blast
Mantle/Intermediate Zone
- Migrating cells that undergo differentiation into neurons and/or glia
- Extend axons away from lumen toward outer surface
- Presumative gray matter
Marginal Zone
- Poor in neuronal cell bodies
- Contain axons that will eventually be myelinated
- Presumative white matter
What happens at the end of the 4th week?
Mantle layer reorganizes into the alar (dorsal) plate and basal (ventral) plate
What connects the Alar Plates?
Roof Plate
What connects the Basal Plates?
Floor Plates
The alar and basal plates undergo differentiation due to what?
Signaling from roof plate and floor plate
What happens to Neuroepithelial cells that migrate from marginal layer -> mantle layer -> ventricular layer -> mantle layer
(1) Neuroepithelial cell migrates from marginal layer to mantle layer
(2) In mantle layer it undergoes mitosis and can differentiate into 1 of the 3 different options:
- Neuron (mantle layer)
- Glioblast (mantle layer)
- Ependymal cell (occurs in ventricular layer)
Mesenchymal cells can differentiate into __ cells
Microglial (this is not a glial or neural cell and thus do not come from the neuroepithelia)
Neurons in dorsal aspect of neural tube become:
Sensory Neurons
Neurons in ventral aspect of neural tube become:
Motor Neurons
Which neurons form first, sensory or motor?
Motor
___ gradient directs neuron identity
SHH
Increased concentrations of SHH:
Motor neurons induced
Decreased concentration of SHH:
Multiple interneurons induced – dependent on decreasing [SHH]
What initiates Ventral specifications of the NT?
SHH secreted by notochord activates NKX2.2 and NKX6.2 to turn on the floor plate to increase the motor neuron identity of the neural tube; gradient forms with higher SHH and motor activation closer to the floor plate
What is the role of NKX2.2 and NKX6.1?
Ventral Neuron formation
SHH is released from what two structures?
(1) Notochord
(2) Floor Plate
What counteracts the SHH gradient?
BMP/TGF-β
What does BMP4 activate?
PAX3 and PAX7
What initiates Dorsal specifications of the NT?
BMP4 and BMP7 (TGF-β family) activated PAX3 and PAX7 in the roof plate to activate dorsal associated neurons (remember they are not sensory themselves b/c sensory nerves are located in the dorsal root ganglion)
Positional changes of the spinal cord from neonate to adult?
- Neonate spinal cord is at the level of L3/L4
- Adult spinal cord stops at L1/L2
Filum Terminale
- Originates at end of Medullary Cone
- Travels down and attaches to C1
Where is the Root of 1st sacral nerve present from embryo to adult?
S1
How are the Intermediate columns formed?
Most dorsal cells of basal plate undergo segregation -> form the intermediolateral cell columns (T1-L3 and S2-S4 only) -> form the lateral horns (autonomic presynaptic cell bodies)
Where are the visceral motor neurons of the sympathetic and parasympathetic divisions located?
- Sympathetic: T1-L3
- Parasympathetic: S2-S4
What forms sensory ganglia in the head?
NCC and ectodermal placodes
What do Neural Crest Cells form in the Trunk?
Sensory neurons in dorsal root ganglions, enteric nervous system, and schwann cells
What do axons pass through to form a ventral root?
Cranial Sclerotome
What do axons from the dorsal root ganglion do?
Extend from dorsal root ganglion to the dorsal horn (sensory nerves are not in the spinal cord themselves, they are stored in the dorsal root ganglion)
What do cranial peripheral neurons consist of?
Sensory and parasympathetic (ANS) components
When do cranial ganglia appear?
End of 4th week to the beginning of the 5th week
What do ectodermal placodes give rise to?
Sensory structures (ears, vision, smell)
What do Trigeminal nerves arise from?
NCC or Ectodermal Placodes
What do CN VII and VIII arise from?
BOTH NCC and Ectodermal Placodes
What is the pathway visceral motor neurons of the ANS in the trunk (both sympathetic and parasympathetic divisions) follow?
Two-chain pathway
(1) Preganglionic neuron and fibers
(2) Ganglionic neuron and postganglionic fibers
(Preganglion fiber from CNS synapses with Postganglionic fiber in the Autonomic Ganglion)
What neurotransmitter is typically released from the preganglionic fiber in the sympathetic NS? Postganglionic fiber in the sympathetic NS?
- Preganglionic: Ach
- Postganglionic: NE
In the ___ pathway, the preganglionic fiber is short & can have multiple targets, synapses in autonomic ganglion on postganglionic fiber that also can have multiple targets
Sympathetic
What neurotransmitter is typically released from the preganglionic fiber in the parasympathetic NS? Postganglionic fiber in the parasympathetic NS?
- Both release Ach
In the ___ pathway, the preganglionic fiber is long & synapses on one target, synapses in autonomic ganglion located in muscle on postganglionic fiber
Parasympathetic
What arises from the neuroectoderm in the ANS?
Preganglionic neurons (sympathetic and parasympathetic)
What arises from the NCC in the ANS?
- Ganglionic neurons and postganglionic fibers
- Sympathetic: trunk and collateral ganglia
- Parasympathetic: CN ganglia in the head and neck, terminal ganglia in the trunk
