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Developmental Neurobiology
Mary Wines-Samuelson
Email: [email protected]
Textbook: Development of the Nervous System
Sanes, Reh, and Harris
Lectures on Blackboard; non-textbook reading materials
NSC 249--first third
Jan. 18: Course overview and a discussion of gene regulation as it applies to neural
development (MWS)
Jan. 23: Neural induction and regionalization I (MWS)
Jan. 25: Neural induction and regionalization II (MWS)
Jan. 30: Neurogenesis, migration and differentiation in the nervous system I (MWS)
Feb. 1: Neurogenesis, migration and differentiation in the nervous system II (MWS)
Feb. 6: Neurogenesis, migration and differentiation in the nervous system III (MWS)
Feb. 8: Regulation of neurogenesis in primate brain (Dr. David Kornack)
Feb. 13: Neurite outgrowth and pathfinding I (MWS)
Feb. 15: Neurite outgrowth II (MWS) end of material for Exam I
Feb. 20: EXAM I
The origins of developmental biology
-Hippocrates in 5th cent BC: “heat,
wetness, solidification”
-Aristotle in 4th cent BC: How are
different parts formed?
a) Preformationism
b) Epigenesis (“upon formation”), or
progression of new structures
*This debate lasted for 1400 years!
FINALLY… cell theory developed (1820-1880)
Schleden (botanist) & Schwann (physiologist): All living things
are derived from cells
Early debates regarding
development centered on
preformationism vs. epigenesis
Homunculus in sperm head (1694) 
Weismann’s mosaic theory
Radical idea: germ cells determine embryo
characteristics (somatic vs. germline)
-believed that nuclei divided asymmetrically to
give rise to lineages with different cell fates…
New debate!
*a botanist monk would show that
chromosomes determine inheritance of traits
(Boveri & Sutton)
Initial experiment by Roux appeared to support the
mosaic model
-”killed” one blastomere  half-embryo; thus,
critical fate determinants missing
Later work by Dreisch was inconsistent with mosaic model
*1st demonstration of regulation: embryo’s ability to
develop normally despite missing or rearranged
Repression of genetic expression can be reversed by
changing the cytoplasmic environment
*Thus, development must also involve some ability of cells to
respond to a new context= plasticity (or adaptability)
*Development = a progression of fate restrictions?
Fate restriction over time during brain development
Correct spatial and
temporal control of
gene expression
and protein
synthesis is
essential during
Genes are turned on/off by protein complexes bound to promoter
Transcription requires: 1) open chromatin conformation state;
2) TATA box for RNA polymerase; 3) activators binding to
enhancer elements in the 5’ UTR; and 4) RNA polymerase.
Regulatory regions (promoters) determine tissue-specific gene
-mouse transgene with GH (pituitary) under the control of the
mouse elastase gene (in pancreas) turns on GH in pancreas
Neural fate determination via: a) extrinsic signal, b)
autocrine/paracrine signal, c) receptor-mediated signal
transduction, & d) intrinsic
Sequestration of
signaling factors
determines fate
after mitosis
Mechanisms of cell fate determination
Direct cell-cell
(lateral) signaling
can occur by:
1) Diffusible ligandreceptor
2) Transmembrane
3) Direct diffusion
of factors across
gap junctions
Glucocorticoid receptor binding to hormone activates nuclear
translocation & transcription
*estrogen/tamoxifen-ER: used to generate inducible transgenics
Another level of control: one TF (gene) can activate or repress
other genes, depending on promoter context
One mode of maintaining gene activation: positive autoregulation
Inducing signals and competent tissue present during gastrulation
*results are time-sensitive!
Heritability: the proportion of phenotypic variance due to
genetic variance
P= G + E;
h2= genotypic variance/phenotypic variance (or g + e)
Localized determinants
and asymmetric cell
divisions establish the
body plan of the early
Gastrulation initiates at the blastopore (posterior), & extends
Neural crest arises from the dorsal seam of the newly-formed
neural tube
Mesoderm induces neural signaling in ectoderm; default is
Spemann and Mangold
implicate the dorsal lip
of the blastopore in
neural induction