CHAPTER 12, THE EMERGENCE OF THE ECTODERM: CENTRAL NERVOUS SYSTEM AND EPIDERMISMajor derivatives of the ectoderm germ layer  Ectoderm basically forms nervous system and epidermis in vertebrate.Major derivatives of the ectoderm germ layerMajor derivatives of the ectoderm germ layerMajor derivatives of the ectoderm germ layerNeurulation in a chick embryo (dorsal view) Flat neural plate with/without underlying notochord Neural groove Migration of endodermal and mesodermal cells through the primitive streak Notochord Neurulation in a chick embryo (dorsal view) Neural tube with three brain regions 24-hours after fertilization Cephalic (head) region in neurulation Caudal (tail) region in gastrulation Neurulation in a chick embryo (dorsal view)12.2 Neurulation in a chick embryo (dorsal view) (Part 4)12.2 Neurulation in a chick embryo (dorsal view) (Part 5)Establishing the Neural Cells  There at at least four stages  Competence  Cells can become neuroblasts  Specification ----------------------------------- reversible  Cells have received the signals  Commitment (determination) ----------------- irreversible  Neuroblasts have entered the neural differentiation  Differentiation  Neuroblasts leave the mitotic cycle and express the characteristic genes Formation of the Neural Tube  Primary neurulation: the neural plate cells form a hollow tube.  Happen in anterior part  Secondary neurulation: the neural tube arises from mesenchyme cells.  Happen in posterior partPrimary neurulation: neural tube formation in the chick embryo MHP: medial hinge point Induction of wedge shape on MHP Primary neurulation: neural tube formation in the chick embryo DLHP: dorsolateral hinge point Induction of wedge shape on DLHP Three views of neurulation in an amphibian embryoThree views of neurulation in an amphibian embryoThree views of neurulation in an amphibian embryoNeurulation in the human embryo Three major site of neural closure Neurulation in the human embryo Stillborn infant Caused by the failure of closing the neural tube. Neural defects are seen in about1 in every 1000 live births. Expression of N- and E-cadherin adhesion proteins during neurulation in Xenopus Interactions of N-cadherin in the neural plate is essential to form the neural tube. Induced N-cadherin by mRNA injection Folate-binding protein in the neural folds as neural tube closure occurs Essential factors for neural tube closure Genetic: Pax3, Sonic hedgehog and openbrain Environmental: folate (vitamin B12) In situ hybridization, mRNA for folate-binding protein Secondary neurulation in the caudal region of a 25-somite chick embryo Happen in posterior part Primary neurulation in anterior by neural plate cells  Secondary neurulation in posterior by mesenchyme cells  Neural tube closure is important.  Key factors for the closure  Genes: Cadherin, Pax3, Sonic hedgehog or openbrain  Diet: Cholesterol or folate (vitamin B12)Early human brain development Anterior-posterior patterning of the nervous system is controlled by Hox genes. Brain ventricle formation in zebrafish Na+/K+ ATPase deficient No brain ventricle & no fluid pressure Dorsal-ventral specification of the neural tubeDorsal-ventral specification of the neural tubeDorsal-ventral specification of the neural tubeDorsal-ventral specification of the neural tube Chick neural tube Chick dorsal neural tube Shh, green; Dorsalin, blue; Motor neurons, orange Pax7, blue; Pax6, green; Nkx6.1, red; Nkx6.1 & Pax6 overlap, yellow.Cascade of inductions initiated by the notochord in the ventral neural tubeCascade of inductions initiated by the notochord in the ventral neural tube Notochord can induce the secondary ventral neural plate Induction of Neural Tube  Need fluid pressure set up by Na+/K+ ATPase  No Na+/K+ ATPase  Anterior-posterior induced by Hox gene complexes  Ventral: Sonic hedgehog from notochord and floor plate  Dorsal: BMPs from ectoderm  Dorsal: TGF-beta family from roof plateNeural stem cells in the germinal epithelium Germinal neuroephithelium – a layer of neural stem cells Differentiation of the walls of the neural tube Spinal cord & Medulla organization Gray matter White matter Development of the human spinal cordDevelopment of the human spinal cordDifferentiation of the walls of the neural tube Cerebellar organization BMP Shh Cerebellar organizationDifferentiation of the walls of the neural tube Cerebral Cortex Neuron-glia interaction Glial Guidance How do the cell know which layer to enter? Determination of cortical laminar identity in the ferret cerebrum Determination is made during the final cell division Older neuronal precursors migrate to farther. Determination of cortical laminar identity in the ferret cerebrum After S phase During S phase Depending on the cell cycle; Foxg1 gene Transplant into older neuronal precursors which send the cells to 2/3 layer. Cell Cycle  G1 phase. The cell grows.  S phase. The cell makes copies of its chromosomes.  G2 phase. The cell checks the duplicated chromosomes and gets ready to divide.  M phase.  Cells that are not dividing leave the cell cycle and stay in G0. Evidence of adult neural stem cells Green, BrdU positive Mouse Human BrdU will be incorporated into a cellular DNA, and it indicates the new DNA replication and mitosis. BrdU is analogue for thymidine. Neural stem cells exist in adults