Development Plasticity and Repair Exam 2 Review Neurogenesis and Migration 1 2 In what brain regions are new neurons being developed into adulthood be sure to include their birthplace as well as where they end up What is the functional role of these new neurons when they have matured Cortical neurons born in the ventricular zone of the telencephalon must migrate towards the outer surface of the brain to build up the six neuronal layers of the adult cerebral cortex New neurons are created in the mammalian olfactory bulb and the hippocampus in the adult brain In the olfactory bulb the new neurons may be required to replace worn out old olfactory sensory neurons The hippocampus is important for formation of memories It contains a small population of adult stem cells that continue to generate new neurons during adulthood The role of neurogenesis in the hippocampus function is not yet clear but it is suggested that new neurons are added to maintain the ability to accumulate memories New olfactory neurons divide in the subventricular zone they move along the rostral migratory stream as they differentiate into neurons Identify and describe a disorder that results from inappropriate or absent neuronal cell migration How does a brain with this disorder differ from a normal brain Lissencephaly is a severe developmental brain disorder in which the folds of the cerebral cortex are either greatly diminished or completely absent In addition the grey matter of the cortex is much thicker in lissencephalic brains it has only four layers instead of six and the majority of the neurons are found in the deepest layers These features indicate that Lissencephaly is due to the failure of cortical neurons to migrate normally 3 Describe in as much detail as possible the three phases of migration the book identifies four I lumped guidance with locomotion as guidance cues are the cues that the cell responds to during locomotion Migration must first be initiated at the point when the cell starts to move The migrating cell must then be guided in the appropriate direction In the final step termination the cell stops once it has reached its destination Initiation of Neural Crest Cell Migration Before they migrate neural crest cells are tightly held together with their neighbors in the neuroectoderm They must therefore become less adhesive and lose their connections to their neighbors before they can emigrate Dynamic changes occur in their expression of cell adhesion molecules like cadherin Many of the cellular changes that occur at this early stage of neural crest cell migration are controlled by the transcription factors Snail1 and Snail 2 which are expressed in response to BMP signaling in the dorsal neural tube In the migration of olfactory precursor cells they first move away from the subventricular zone where they are born and enter the rostral migratory stream Several secreted factors have been shown to be involved in initiating their movement these include motogenic factors such as secretory protein MIA which is produced by glial cells surrounding the migratory olfactory precursors and the secreted signaling molecules Slit1 and Slit2 are also produced by cells surrounding the SVZ How are migrating cells guided to their destinations The two major mechanisms that have so far been shown to guide the direction of migrating neurons are chemotaxis and guidance by a glial scaffold In chemotaxis the movement of a cell is directed by a chemical signal cells either move towards such signals known as chemoattraction or away from them known as chemorepuslion Cells known to be guided by chemotaxis in the developing nervous system include specific neural precursors in C elegans neural crest cells and the cells that form the lateral line in zebra fish In contrast many migrating cortical neurons receive their directional guidance from radial glial cells Directional Migration of Neurons in C elegans One pair of neural progenitors known as Q cells arise at equivalent positions on either side of the embryo QL on the left and QE on the right During normal development the Q cells and their descendants migrate in opposite directions QL and its descendants migrate towards the posterior of the embryo while QE and its descendants migrate anteriorly towards the head However in certain mutant strains of C elegans in which Wnt signaling is defective both QR and QL lose their directional migration and each migrates randomly along the anteroposterior axis Three Wnt genes are expressed in a gradient in the C elegans embryo with high levels posteriorly and low levels towards the anterior of the embryo Migrating Q cells therefore appear to be guided by responding differentially to the gradient of Wnt expression a In the wild type embryo QR and HSN progenitors migrate anteriorly while QL progenitors migrate posteriorly Three different Wnt genes cwn 1 egl 20 and lin 44 are expressed in a gradient purple with highest levels found at the posterior of the embryo b In mutant embryos that lack expression of either a Wnt or the Wnt receptor lin 17 QL and QR cells migrate randomly along the anteroposterior axis Many C elegans genes are named for the phenotype identified during the genetic screen in which the genes were first identified Thus lin genes show defects in cell lineage while egl genes have defects with egg laying When these genes were subsequently cloned and sequenced it emerged that egl 20 and lin 44 encode Wnts while lin 17 encodes a Wnt receptor frizzled Guidance of Neural Crest Cell Migration Neural crest cells express specific cell surface receptors that allow them to respond to permissive and repulsive cues that guide them on their journey Many neural crest cells migrate along paths that are organized segmentally In the trunk region of the embryo migrating neural crest cells stream over the somites blocks of mesodermal tissue adjacent to the neural tube that will give rise to skeletal muscle and vertebrae While neural crest cells are generated all along the anteroposterior axis of the neural tube they migrate only over the anterior half of each somite avoiding the posterior half Migrating neural crest cells express members of the Eph family of tyrosine kinase receptors and corresponding ephrin ligands are expressed in posterior parts of each somite Repulsive interactions mediated by Eph ephrin signaling confine migrating neural crest cells to the anterior half of each somite Two other families of signaling molecules involved in