Download ppt

Survey
yes no Was this document useful for you?
   Thank you for your participation!

* Your assessment is very important for improving the work of artificial intelligence, which forms the content of this project

Document related concepts

Sonic hedgehog wikipedia, lookup

Hedgehog signaling pathway wikipedia, lookup

Amitosis wikipedia, lookup

Signal transduction wikipedia, lookup

List of types of proteins wikipedia, lookup

Cellular differentiation wikipedia, lookup

JADE1 wikipedia, lookup

Transcriptional regulation wikipedia, lookup

Gene regulatory network wikipedia, lookup

Silencer (genetics) wikipedia, lookup

Transcript
BCS/NSC 249
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
parts
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
development
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
expression
-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
determinant
Sequestration of
signaling factors
determines fate
after mitosis
Mechanisms of cell fate determination
Direct cell-cell
(lateral) signaling
can occur by:
1) Diffusible ligandreceptor
interaction
2) Transmembrane
ligand-receptor
interaction
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
embryo
Gastrulation initiates at the blastopore (posterior), & extends
anteriorly
Neural crest arises from the dorsal seam of the newly-formed
neural tube
Mesoderm induces neural signaling in ectoderm; default is
epidermis
Spemann and Mangold
implicate the dorsal lip
of the blastopore in
neural induction