Lecture 6: Mechanisms of Development Flashcards
What mechanisms drive development?
Genes
cell-cell communication
what is a homologous gene?
a gene similar in structure, evolutionary origin, and likely function, to a gene in another species
What is the concept of genomic equivalence?
all somatic cells have the same chromosomes (set of genes) as all other somatic cells
What does somatic nuclear transfer mean?
cloning
What does somatic nuclear transfer provide evidence for?
genomic equivalence (all cells have same genes)
In the first cloning project, what was fused?
nuclear donor: mammary gland cell nucleus
oocyte donor: enucleated oocyte
T/F: The nuceli of adult somatic cells contain all of the genes necessary to generate an adult organism
True
What is the concept that says the genetic material is the same in every cell, but only a small % of the genome is expressed in each cell type?
Differential gene expression
What are the four levels of gene expression regulation?
differential gene expression
selective nuclear RNA processing
selective mRNA translation
differential protein modification
What technique is used to determine the locations of mRNA expression?
RNA in situ hybridization
What are the 4 cellular processes through which differential gene expression is achieved?
- cell proliferation - producing many cells from one
- cell specialization - creating cells with different characteristics at different positions
- cell interactions: coordinating the behavior of one cell with that of its neighbors
- cell movement: rearranging cells to form structured tissues and organs
In cell induction, what do the inducer and responder do?
inducer - provides signal which changes behavior of target tissue
responder - tissue being induced
what must the responder have in cell induction?
competence - ability to respond to signal
What is an example of a cell induction system?
optic vesicle inducer
Xenopus laevis
How does the optic vesicle inducer in Xenopus work?
optic vesicle inducer indices lens formation in the anterior (head) portion of the ectoderm
cannot do so in the trunk or abdomen (tissues are not competent)
In the optic vesicle inducer in Xenopus, what happens if the optic vesicle is removed?
Surface ectoderm forms abnormal lens or no lens
What role does Pax6 play in Xenopus?
makes ectoderm competent to respond to signals from the optic vesicle (inducer)
What is the competence factor in Xenopus’s optic vesicle induction?
Pax6
What does a homozygous loss of Pax6 lead to?
fatal
almost complete failure of entire eye formation
What is aniridia?
heterozygous mutation to Pax6
not fatal
ocular defects
What is juxtacrine signaling?
contact between inducing and responding cells
what is paracrine signaling?
diffusion of inducers from one cell to another
what are morphogens?
paracrine signaling moleculces which cause concentration-dependent effects
How was the morphogenic property of Nodal identified?
Nodal mRNA injected into embryo
nodal protein is produced - secreted, allowed to signal
mark particular regions/structures, analyze induction
What does it signify if types of genes turned on are dependent on the distance from the source cell?
morphogen is functioning
In a signal transduction cascade, what does a cytoskeleton effector protein do?
alter cell shape or movement
In a signal transduction cascade, what does a gene regulatory effector protein do?
alter gene expression
In a signal transduction cascade, what does a metabolic enzyme effector protein do?
alter metabolism
How is a signaling cascade initiated?
Extracellular signaling molecule binds to receptor
Receptor undergoes conformational change
What are three molecules in the TGFb (Transforming Growth factor b) signaling pathway?
TGFb
BMP
Nodal
Describe the TGFb signaling pathway
secreted molecules (TGFb, BMP, Nodal) bind receptors
Smad proteins are phosphorylated
Smad proteins enter nucleus and modulate txn
What is the sonic signaling pathway involved in?
development
Describe the sonic hedgehog signaling pathway
SHH binds PTCH receptor
SMO no longer inhibited
GLI-mediated txn activated
what happens in the absence of the SHH
PTCH protein inhibits SMO
GLI-mediated txn is repressed
Antagonistic activities of what two signaling pathways pattern the developing spinal chord?
SHH and Wnt/BMP
What patterns the neural tube?
morphogen gradients of SHH And Wnt/BMP
What is situs solitus?
Normal orientation of internal organs
What is situs invertus totalis?
complete mirror reversal of organ LR asymmetry
What is heterotaxy or situs ambiguus?
LR asymmetry of a subset of organs
What does heterotaxy result it?
congenital malformations
what is asplenia?
right isomerism heterotaxy - two of the right side
what is polysplenia?
left isomerism heterotaxy - two of the left side
what congenital diseases can come with LR asymmetry (heterotaxy)?
congenital heart defects
asplenia or polysplenia
malrotaton of intestine, volvulus
What is volvulus? What does it result from?
twisted bowl –> obstruction
from heterotaxy
What are the steps in the development of cardiac LR asymmetry?
L and R-sided bilateral heart fields fuse to form linear heart tube
rightward cardiac looping
growth, additional shaping
what does rightward cardiac looping achieve?
aligns chambers and vascular connections
What gene is expressed asymmetrically in the organizer/node region during development in mice, chicks, frogs, and zebrafish?
Nodal
what are the three symptoms of Kartagener’s syndrome?
immobile sperm –> infertile
chronic bronchitis and sinusitis
some have inverted internal organs
What is immobile in Kartagener’s syndrome?
cilia
Based on Kartagener’s syndrome, how is asymmetry achieved during embryogenesis?
asymmetric fluid flow from cilia establishes morphogen gradient
Describe the Nodal signaling cascade in the lateral plate mesoderm
asymmetric signals (Ca2+ ion) respond to cilia-driven fluid flow
signals trigger nodal expression in left lateral plate mesoderm
Nodal induces txn of Pitx2 (txn factor) and Lefty (Nodal inhibitor)
Where is transcription factor Pitx2 found? What is it thought to do?
left side of developing heart, gut, and brain
regulate expression of genes which mediate asymmetric organ morphogenesis
