Formation of the Nervous System

& Epidermis I

Fates of Ectoderm

• A portion of dorsal ectoderm is specified to become neural ectoderm - cells become columnar in shape

– This region is called the neural plate

• Neurulation is the process by which this tissue forms the neural tube

– Embryo is called the neurula

• Neural tube will form the brain anteriorly and the spinal cord

Derivatives of Ectoderm

Formation of the Neural Tube

• Two majors ways to form the neural tube

– Primary neurulation - cells surrounding the neural plate direct the neural plate cells to proliferate, invaginate and pinch off from the surface to form a hollow tube

– Secondary neurulation - the neural tube arises from a solid cord of cells that sinks into the embryo and subsequently hollows out to form a hollow tube

Neurulation in Various Vertebrates

• Fish - exclusively secondary

• Birds - anterior portion of the neural tube - primary - caudal to the 27th somite pair - secondary

• Amphibians - most by primary neurulation except the tail which is secondary

• Mice - secondary begins at about the 35th somite pair

Primary Neurulation

• Ectoderm divides into three sets of cells

– 1. internally positioned neural tube - brain and spinal cord

– 2. externally positioned epidermis of the skin

– 3. neural crest cells - form in the region that connects the neural tube and the epidermis - but migrate elsewhere

• Form peripheral neurons, glia, skin pigment cells and others

Primary Neurulation

• The process is similar in amphibians, reptiles, birds and mammals

• Shortly after the formation of the neural plate - edges thicken and move upward to form neural folds

• While the neural folds forms - a U-shaped neural groove appears in the center of the plate, dividing future right & left sides of the embryo

Primary Neurulation

• The neural folds migrate toward the midline - eventually fusing to form the neural tube - beneath the overlying ectoderm

• Cells of the dorsal most portion of the neural tube become the neural crest cells

Neurulation in the Chick

Neural Tube Formation

Neural Tube Formation

Neurulation in Amphibians

Primary Neurulation

• Head & trunk regions undergo variants of primary neurulation

– Can be divided into four distinct but spatially and temporally overlapping stages

1 formation of neural plate

2. shaping of the neural plate

3. bending the neural plate to form the neural groove

4. closure of the neural groove to form the neural tube

Formation and Shaping of Neural Plate

• Neural plate formation begins the process of neurulation

– Dorsal mesoderm and pharyngeal endoderm in the head region signals ectoderm to elongate - get columnar neural plate cells

– About 50% of the ectoderm is included in the neural plate

– In amphibians & amniotes - neural plate lengthens & narrows by convergent extension, intercalating several layers into a few layers

• Cell divisions of the neural plate cells are preferentially in the rostral-caudal direction

Bending of the Neural Plate

• Bending of the neural plate involves hinge regions - where it contacts other surrounding tissues

• Here presumptive epidermal cells adhere to the lateral edges of the neural plate & move them toward the midline

– In birds & mammals the cells are called - medial hinge point (MHP) cells

– Derived from the plate just anterior to Hensen’s node and from the anterior midline of Hansen’s node

– The MHP cells anchor to the notochord below & form a hinge - this forms a furrow at the midline

Bending of the Neural Plate

• Notochord induces MHP cells to decrease their height - become wedge shaped

• Then dorsolateral hinge points (DLHPs) - anchored to the surface ectoderm of the neural folds - these cells also become wedge shaped

• After initial furrowing of the neural plate - the plate bends around the hinge regions

• Each hinge is acting as a pivot that directs the rotation of cells around it

• Surface ectoderm helps by pushing toward the midline - helps bend the neural tube

Closure of the Neural Tube

• Neural tube closes as the paired neural folds are brought together at the dorsal midline

• The folds adhere to each other

• In birds the neural crest cells do not migrate from the dorsal region until after the neural tube has been closed at that site

• In mammals, cranial neural crest cells (facial & neck structures) migrate while the folds are elevating - in spinal cord region neural crest cells wait until tube closure to migrate

Closure of the Neural Tube

• Closure along the whole tube is not simultaneous

– Occurs in both directions - ” Zips shut”

• In chicks - neurulation in the cephalic region is well advanced over more caudal areas where gastrulation is still occurring

• Regionalization of the neural tube occurs - results in changes in the shape of the neural tube - beginnings of the various brain compartments

• Openings - anterior neuropore & posterior neuropore

24-hour Chick Embryo

Closure of the Neural Tube

• In mammals - closure initiated at several points along the anterior-posterior axis

• Neural tube defects - failure to close various portions of the tube

– Spina bifida - failure to close the posterior neural tube region at day 27 (or rupture thereafter)

– Severity depends upon how much cord is exposed

– Anencephaly - failure to close the anterior portion of the neural tube

• Fetal forebrain & vault of the skull fail to form

Neurulation in Humans

Closure of the Neural Tube

• Neural tube defects occur in 1 in 500 live births

• Human closure - interplay of genetic & environmental factors

• The Pax3, sonic hedgehog & openbrain - essential for neural tube formation

• Cholesterol & folic acid (Vit B₁₂) - critical for neural tube formation

• Neural tube eventually separates from surface ectoderm due to expression of different adhesion molecules

– Change from E-cadherin to N-cadherin

Expression of N & C-Cadherins in Neurulation

Secondary Neurulation

• Involves the making of a medullary cord & its subsequent hollowing into a neural tube

• In frogs and chicks - secondary neurulation - seen in the neural tube of the lumbar (abdominal) and tail vertebrae

• Considered as a continuation of gastrulation - in the frog, instead of involuting into the embryo, the cells of the dorsal blastopore lip keep growing ventrally

Secondary Neurulation in 25 Somite Chick

Secondary Neurulation

• This ventral growing region - chordoneural hinge - contains precursors for both the posteriormost portion of the neural plate and the posteriormost portion of the notochord

– Growth of this region - creates a linear tadpole

– Tip of the tale - a direct descendant of the dorsal blastopore lip

– The cells lining the blastopore form the neurenteric canal

• Proximally - fuses with the anus

• Distal portion - becomes ependymal canal - lumen of the neural tube

Secondary Neurulation in Xenopus