Page 1Page 2Page 3Page 4Page 5Page 6Page 7Page 8Biology 4361Developmental BiologyGilbert Ch. 12. The Emergence of the Ectoderm: Central Nervous System and EpidermisNovember 30, 2006Establishing the Neural Cells - neural plate - portion of the dorsal ectoderm specified to become neural ectoderm- distinguishable by columnar appearance of cells - neurulation - process of forming the neural tube- neural tube forms the brain anteriorly and the spinal cord posteriorly - neurula - embryonic stage of neural developmentneural cells become specified though their interactions with other cells - pluripotent cells of the epiblast or blastula become neural precursor cells - neuroblasts - stages include:- competence - cells can become neuroblasts with proper signals- specification - cells have received signals to become neuroblasts, but fate can be alteredby other signals (e.g. repressive or inhibitory signals)- commitment (or determination) - neuroblasts have entered differentiation pathway andwill become neurons even in the presence of inhibitory signals- differentiation - neuroblasts leave the mitotic cycle ; express genes characteristic ofneuronsFormation of the Neural Tube - two ways of converting neural plate into neural tube: - primary neurulation - neural plate cells form hollow tube- secondary neurulation - neural plate cells form solid cord; subsequently hollows out - in general, anterior portion of neural tube is made by primary neurulation; posterior bysecondary neurulationPrimary neurulation - ectoderm can be divided into three sections:- internally positioned neural tube- forms brain and spinal cord- externally positioned epidermis- forms skin- neural crest cells- form in the region connecting the neural tube and epidermis- migrate to new locations- generate peripheral neurons, glia, pigment cells, others - primary neurulation appears similar in all vertebrates: - summary example - amphibians:- shortly after neural plate formation, edges thicken; move upward to form neuralfolds- U-shaped neural groove appears in center of plate- folds migrate to the midline of the embryo- fuse and form tube beneath the overlying epidermis Details: four distinct, but spatially and temporally overlapping stages:- formation of the neural plate- shaping of the neural plate- bending of the neural a plate to form the neural groove- closure of the neural groove to form the neural tube FORMATION AND SHAPING OF THE NEURAL PLATE- dorsal mesoderm and pharyngeal endoderm in the head region signal ectoderm above toelongate into columnar neural plate cells- as much as 50% of ectoderm is included in neural plate- neural plate lengthens along the AP axis- mechanism: convergent extension; intercalating several layers into a few layers- also, preferential division along rostral-caudal (beak-tail; anterior-posterior) axis BENDING OF THE NEURAL PLATE- hinge regions form; - in birds and mammals, cells at midpoint of neural plate form the medial hingepoint (MHP) cells- MHP cells anchor to the notochord- notochord induces MHP cells to decrease height and become wedge-shaped- dorsolateral hinge points (DLHPs)- two hinge regions form furrows near the connection of the neural platewith the remainder of the ectoderm- anchored to surface ectoderm- decrease height, become wedge shaped- after initial furrowing of the neural plate, plate bends around hinge regions- hinges act as pivots that direct the rotation of the cells around it- also, surface ectoderm of chick embryo pushes toward the midline- neural plate anchored to underlying mesoderm- motive force by ectoderm produces inward folding movement CLOSURE OF THE NEURAL TUBE- paired neural folds brought together; adhere; merge- closure is not simultaneous or continuous throughout the tube; e.g. in vertebratesinduction of the head starts before induction in the posterior regions- 24 h chick - neurulation in cephalic region is well advanced, while caudal regionis still undergoing gastrulation- two open ends of the neural tube are:- anterior neuropore- posterior neuropore- mammals - neural tube closure in initiated ast several places along the A-P axis- humans - probably 3 closure initiation sites- neural tube defects are caused by failure of closure at a given site- in humans, ~ 1/1000 births have some for of NTD- spina bifida - failure to close the posterior neuropore (~ d 27)- severity depends on how much spinal cord is exposed- anencephaly - failure to close the anterior neuropore- forebrain exposed to amnionic fluid and subsequently degenerates- craniorachischisis – failure of entire neural tube to close- neural tube forms a closed cylinder that separates from the surface ectoderm- separation mediated by the expression of different cell adhesion molecules- cells that become neural tube originally express E-cadherin (epidermal); but stopexpression and shift to N-cadherin (N-CAM)- as a result, neural tube and epidermal cells no longer adhere to each other- neural tube closure (humans) is dependent on mixture of intrinsic (i.e. gene products)and extrinsic (i.e. nutritional/environmental) factors- requires Pax3, Sonic hedgehog, openbrain12- dietary factors, e.g. cholesterol, folic acid (folate, vitamin B ) also essential- role of folate not completely understood, but folate receptors appear tobe present on the dorsalmost regions of mouse neural tube- natural antibodies to folate receptor have been associated withneural tube defects in humans- also plant-derived or anthropogenic teratogens may play a roleSecondary neurulation - segregation of cells from prospective epidermis and prospective gut tissue form prospectivemedullary cord beneath the surface ectoderm- followed by cavitation of central portion of cored into several hollow spaces- cavities coalesce into single cavityDifferentiation of the Neural TubeDifferentiation occurs simultaneously on three different levels: - gross anatomical level: neural tube and its lumen bulge and constrict to form the chambers ofthe brain and spinal cord - tissue level: cell populations withing the wall of the neural tube rearrange themselves to formthe different functional regions of the brain and spinal cord - cellular level: neuroepithelial cells differentiate into numerous types of nerve cells (neurons)and supportive cells (glia)The anterior-posterior axis - early neural tube is a straight structure - anterior of the tube balloons into three primary vesicles - forebrain