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