CHAPTER 12, THE EMERGENCE OF THE ECTODERM: CENTRAL NERVOUS SYSTEM AND EPIDERMISDetermination of cortical laminar identity in the ferret cerebrum Determination is made during the final cell division Older neuronal precursors migrate to farther. Depending on the “Birthday”, the final destination is determined 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. Differentiation of Neurones Differentiation of Neuroepithelial cells  From Neuroepithelial  Ventricular (ependymal) cells --- neural tube lining secreting the cerebrospinal fluid.  Precursors of the neurons --- conduct electric potentials  Precursors of the glial cells --- aid in the construction of the nervous system. Diagram of a motor neuron Dendrites --- pick up electric impulses from other cells Axon --- extend for several feet Synapses Axon growth cones Green, actin; Red, tubuline Nerve outgrowth is led by the tip of axon, growth cone. Myelination in the central and peripheral nervous systems  Myelination --- part of axon is insulated at intervals by glial cells, oligodendrocyte.  Myelin sheath  Schwann cell Progression of myelination over the cortical surface during adolescence in human brain Magnetic resonance imaging (MRI) The teenage brain is a complicated and dynamic entity, and (as any parent knows) one that is not easily understood. But if one survives these years, the resulting adult brain is usually capable of making reasoned decisions, even in the onslaught of emotional situations. • The dynamics of optic development • Neural retina differentiation • Lends and cornea differentiation Development Of The Vertebrate Eye Ectodermal competence and the ability to respond to the optic vesicle inducer in Xenopus Only the head ectoderm is competent to respond to the signal from the optic vesicle by producing a lens. Induction of optic and nasal structures by Pax6 in the rat embryo Wild-type Pax6 mutant Day 12 of gestation Newborn Defective component – the optic vesicle or the surface ectoderm? Recombination experiments of optic vesicles and surface ectoderm The induction deficiency of Pax6-deficient rats is caused by the inability of the surface ectoderm to respond to the optic vesicle. Pax6 is needed for the competence on the surface ectoderm. Sequence of lens induction in amphibians Induction by pharyngeal endoderm & heart-forming mesoderm Induction by anterior neural plate inducing Pax6 Optic vesicle secretes BMP4 (inducing Sox2 & Sox3 in perspective lens) & Fgf8 (inducing L-Maf in perspective lens). The combination of Pax6, Sox2, Sox3 and L-Maf in the endoderm ensures the production of the lens. Schematic diagram of the introduction of mouse lens Embryonic day 9 early late Thickening Optical cup day 10 Invaginate Schematic diagram of the introduction of mouse lens Lens vesicle day 11 day 13 Lens differentiation Summary of the inductive interactions on eye development Sonic hedgehog separates the eye field into two bilateral fields Control Scanning electron micrograph 10 µM Jervine (a potent teratogen; a sonic hedgehog (Shh) pathway inhibitor) Olf, olfactory processes; Opt, optic vesicles Cyclopia – a single eye in the center of the face, usually below the nose. Sonic hedgehog separates the eye field into two bilateral fields 12-day mouse embryo Source of Shh Endoderm Surface-dwelling and cave-dwelling Mexican tetras (Astayanax mexicanum) Ptc2 & Pax2 respond to Shh protein. In broader domain, Surface < Cave Optic vesicle Size: Surface > Cave Pax2: Surface < Cave Too much hedgehog protein suppress Pax6 expression. Arrest eye development Expression of the Rx genes in vertebrate retina development Neurula Newly hatched tadpole Single eye field Two developing retina Rx: retinal homeobox Expression of the Rx genes in vertebrate retina development Rx gene KO mouse Mutant Rx gene Pax6 and Six3 continued expression in the retinal progenitor cells requires Rx protein. • Pax6: specification of the retinal ganglial cells. • Six3: coordinating the number of divisions taken by the retinal precursor cells. Retinal neurons sort out into functional layers during developmentDifferentiation of the lens and the anterior portion of the mouse eye Embryo day-13 Embryo day-14 The lens vesicle detaches from surface ectoderm and has invaginated into the optic cup. The lens is filled with crystallin-synthesizing fibers. Several layers of the mesenchyme cells. Differentiation of the lens and the anterior portion of the mouse eye Embryo day-15 Embryo day-15.5 The lens detaches from the corneal layers, generating an anterior cavity. Corneal layers differentiate and begin to become transparent. Close binding of Sox2 and Pax6 on the crystalline enhancer• The origin of epidermal cells • Cutaneous appendages • The follicular stem cell The Epidermis and the origin of cutaneous structures The origin of epidermal cells  The skin is composed of a lower dermis and an outer epidermis.  Dermis – developed from mesoderm  Epidermis – developed from ectoderm Layers of the human epidermis  Basal layer contains the epidermal stem cells dividing to continuously replace the upper layer.Growth factors for the epidermis development  TGF-α, transforming growth factor-α --- made by basal cells; stimulate own division by the autocrine.  KGF, keratinocyte growth factor (or Fgf7) --- made by dermis; regulate the migration and differentiation of the epidermal cells by the paracrine, Cutaneous appendages  Cutaneous appendages: hairs, scales or feathers Early development of the hair follicle and hair shaft Placodes secrete Wnt protein Wnt signaling is critical for the initiation of follicle development. Dermal signals stabilize β-catenin in ectoderm. Early development of the hair follicle and hair shaft Engulfing the dermal papilla Forming sebaceous gland Localizing the sebaceous gland on the lateral wall Early development of the hair follicle and hair shaft  Migration and lineage of the epidermal stem cells to the bulge The Follicular stem cells  The bulge retains the epidermal stem cells.  Regenerating the hair shaft.  Paracrine factors near bulge  Fgf18 & BMP6  The bulge is not monitored by the immune system.