Module 5: Lecture chapter 18 Flashcards
Overview
Instructions in the genome establish the developmental fate of cells in multicellular organisms.
Developmental pathways consist of sequences of distinct regulatory steps.
The zygote is totipotent, giving rise to all body cells.
Gradients of maternally-derived regulatory proteins establish polarity of the body axis and control transcriptional activation of zygotic genes.
Transcriptional regulation and cell signaling mediate development in animals and plants.
The same set of genes appears to regulate early development in all animals.
Gradients of Maternally-derived regulatory proteins establish _____ and control _____.
Gradients of maternally-derived regulatory proteins establish Polarity of the Body Axis and control Transcriptional Activation of Zygotic Genes.
_____ and ____ mediate development in animals and plants.
Transcriptional regulation and cell signaling mediate development in animals and plants.
The same set of genes appears to regulate early development in _____.
The same set of genes appears to regulate early development in ALL Animals.
Development
In multicellular organisms, life begins as a single cell.
With few exceptions, somatic cells contain the same genetic information as the zygote.
In development, cells commit to specific fates and differentially express subsets of genes.
Cells identify and respond to their position in developmental fields.
Daughter cells may differ with respect to regulatory instructions and developmental fate.
With few exceptions, _____ contain the same genetic information as the ____.
With few exceptions, somatic cells contain the same genetic information as the zygote.
Building the embryo:
Developmental decisions
made at specific times during development
many are binary, e.g., male or female
most are irreversible
many involve groups of cells rather than single cells
Most decisions involve changes in transcription
Building the embryo:
In animals, decisions are made to
establish anterior-posterior and dorsal-ventral axes
subdivide the anterior-posterior axis into segments
subdivide dorsal-ventral axis into GERM layers
produce various tissues and organs
*Most decisions involve changes in transcription
Most decisions involve changes in ______ .
Most decisions involve changes in transcription
Development and the Genome:
- Animal genomes contain tens of thousands of genes, but only a fraction of them control the developmental process
- Development is the attainment of a differentiated state by all cells of an organism
Development is ……
the attainment of a differentiated state by all cells of an organism
According to the ______, development and differentiation is accomplished by activating and inactivating genes at different times and in different cell types.
According to the Variable Gene Activity hypothesis, development and differentiation is accomplished by activating and inactivating genes at different times and in different cell types.
According to the variable gene activity hypothesis, development and differentiation is accomplished by _______ .
According to the variable gene activity hypothesis, development and differentiation is accomplished by activating and inactivating genes at different times and in different cell types.
Early stages of embryonic development in Drosophila.
(a) Fertilized egg with zygotic nucleus (2n), shortly after fertilization.
(b) Nuclear divisions occur about every 10 minutes.
9 rounds of division produce a multinucleate cell, the Syncytial Blastoderm.
(c) At the 10th division, the nuclei migrate to the periphery (a.k.a., the cortex) of the egg.
Then 4 additional rounds of nuclear division occur.
A small cluster of cells, the Pole Cells, form at the posterior pole about 2.5 hours after fertilization.
These cells will form the germ cells of the adult.
(d) About 3 hours after fertilization, the nuclei become enclosed in membranes, forming a single layer of cells over the embryo surface, creating the cellular blastoderm.
(e) At about 10 hours after fertilization, the segmentation pattern of the body is clearly established.
Behind the segments that will form the head, t1–t3 are thoracic segments, and a1–a8 are abdominal segments.
(f ) The adult fly showing the structures formed from each segment of the embryo.
Early stages of embryonic development in Drosophila.
Reworded…
- Diploid zygote nucleus is produced by fusion of parental gamete nuclei.
- 9 rounds of nuclear divisions produce a multinucleated Syncytium.
- Approximately 4 more divisions occur at the cell Periphery.
Pole cells form at the posterior pole (precursors to germ cells). - Nuclei become enclosed in membranes, forming a single layer of cells over embryo surface.
- Embryo
- Adult
Early stages of embryonic development in Drosophila.
Simplified…
- Single-celled diploid
- Multinucleate Syncytium
- Syncytium Blastoderm with Pole Nuclei clustered at posterior end.
- Cellular Blastoderm
master regulatory gene:
necessary and sufficient to determine cell fate
morphogen:
master regulator that determines fate at 3 or more concentrations!
a morphogen is a master regulator that…..
determines fate at 3 or more concentrations!
maternal vs zygotic genes
Maternal genes: gene products are expressed during oogenesis and deposited in the egg; hence expression of maternal gene products is based on genotype of mother!
Zygotic genes: gene products are expressed in the zygote (fertilized egg); hence expression of zygotic gene products is based on genotype of the zygote!
Maternal genes:
gene products are expressed during oogenesis and deposited in the egg.
Expression of maternal gene
products is based on genotype of mother!
Zygotic genes
gene products are expressed in the zygote (fertilized egg).
Expression of zygotic gene products is based of genotype of the zygote!
Drosophila anterior-posterior axis
Determined by gradients of BCD (product of bicoid) and HB-M (product of hunchback)
- mRNA is maternally deposited into the egg
- BCD mRNA is tethered to “–” ends of microtubules via 3’ UTR
- HB-M protein gradient depends on NOS protein
- nos mRNA tethered to “+” end of microtubule via 3’ UTR
- NOS protein gradient blocks translation of hb-m mRNA, resulting in HB-M gradient
Resulting gradients of BCD and HB-M determine axis
The Drosophila anterior-posterior axis is determined by……
gradients of BCD (product of bicoid) and HB-M (product of hunchback)
HB-M protein gradient depends on _____ .
NOS protein
nos mRNA is tethered to the ….
“+” end of the microtubule via 3’ UTR
BCD mRNA is tethered to the….
“–” ends of microtubules via 3’ UTR.
NOS protein gradient blocks translation of _____, resulting in ____ .
NOS protein gradient blocks translation of hb-m mRNA, resulting in HB-M gradient
Bicoid
a morphogen that determines cell fate.
The Drosophila dorsal-ventral axis is determined by the ……
gradient of transcription factor DL (encoded by dorsal)
Determined by gradient of transcription factor DL (encoded by dorsal)
gradient established by interaction of spz and Toll gene products deposited in oogenesis and released during embryogenesis
SPZ-TOLL complex triggers signal transduction pathway in cells that phosphorylates inactive DL
Phosphorylated DL migrates to nucleus, activating genes for ventral fates
In the Drosophila dorsal-ventral axis, the gradient is established by interaction of ___ and ___ gene products deposited in ____ and released during _____.
In the Drosophila dorsal-ventral axis, the gradient is established by interaction of spz and Toll gene products deposited in oogenesis and released during embryogenesis
In the Drosophila dorsal-ventral axis, the SPZ-TOLL complex triggers ______ in cells that phosphorylate _____.
In the Drosophila dorsal-ventral axis, the SPZ-TOLL complex triggers Signal Transduction Pathway in cells that phosphorylate Inactive DL.
Phosphorylated DL migrates to nucleus, activating genes for ____ fates.
Phosphorylated DL migrates to nucleus, activating genes for ventral fates
Positional information
Localization of mRNAs within cell establishes positional information in cases where developmental fields begin as a single cell
Formation of concentration gradients of diffusible molecules establishes positional information in developmental fields
Such diffusible developmental regulatory molecules are known as morphogens
Localization of _____ within cell establishes positional information in cases where developmental fields begin as a _____ .
Localization of mRNAs within cell establishes positional information in cases where developmental fields begin as a single cell
Formation of _____ establishes positional information in developmental fields.
Such diffusible developmental regulatory molecules are known as _____.
Formation of concentration gradients of diffusible molecules establishes positional information in developmental fields
Such diffusible developmental regulatory molecules are known as morphogens.
Complex pattern: Drosophila
Successive interpretation of established, changing, and new gradients
Largely due to changes in transcription
Genes targeted by gradients of maternal A-P and D-V transcription factors are cardinal genes
- respond to these factors at enhancers and silencers
- similar genes in other animals
Genes targeted by gradients of maternal A-P and D-V transcription factors are ____ .
Genes targeted by gradients of maternal A-P and D-V transcription factors are Cardinal Genes
cardinal genes
Genes targeted by gradients of maternal A-P and D-V transcription factors are cardinal genes
They respond to these factors at enhancers and silencers.
There are similar genes in other animals.
Drosophila development
Developmental fate determined through transcription-factor interactions
A-P cardinal genes = gap genes
Bifurcation of development: targets of gap gene encoded transcription factors
Bifurcation of development
targets of gap gene encoded transcription factors
- one branch to establish correct number of segments
- one branch to assign proper identity to each segment
A-P cardinal genes
= gap genes
Kruppel and knirps (mutants have gap in normal segmentation)
promoters have differential sensitivity to BCD and/or HB-M
establishes different developmental fields along embryo, roughly defining segments
Segment number
gap gene products activate several different pair-rule genes
expression produces repeating pattern of 7 stripes, each offset
pair-rule products act combinatorially to regulate transcription of segment-polarity genes
expressed in offset pattern of 14 stripes
gap gene products activate ______
pair-rule genes
- several different pair-rule genes
- expression produces repeating pattern of 7 stripes, each offset
pair-rule products act combinatorially to regulate …..
Transcription of Segment-Polarity genes
- expressed in offset pattern of 14 stripes
Segment identity
gap gene products target cluster of homeotic gene complexes
- encode homeodomain transcription factors
- mutations alter developmental fate of segment
e.g., Bithorax (posterior thorax & abdomen) and Antennapedia (head and anterior thorax)
_____ products target cluster of homeotic gene complexes
gap gene products target cluster of homeotic gene complexes
- encode homeodomain transcription factors
- mutations alter developmental fate of segment
Pattern formation
Transcriptional response to gradients (asymmetrical distribution) of transcription factors
Memory of cell fate
Cell-cell interactions
Memory of cell fate
- intracellular and intercellular positive-feedback loops
e. g., homeodomain protein binds to enhancer elements of its own gene, ensuring continued transcription - Pattern formation
Cell-cell interactions
- inductive interaction commits groups of cells to same developmental fate
- lateral inhibition results in neighboring cells assuming secondary fate
results in neighboring cells assuming secondary fate.
lateral inhibition
5 Generalizations
Asymmetry of maternal gene products establishes positional information used for early development
Successive rounds of expression of genes encoding transcription factors establish axes and body part identity
Positive feedback loops maintain differentiated state
Components of one developmental pathway are also found in many others
Differences in types and concentrations of transcription factors result in different outputs
______ of maternal gene products establishes positional information used for early development.
Asymmetry of maternal gene products establishes positional information used for early development.
______ maintain differentiated state
Positive feedback loops maintain differentiated state
Developmental parallels
Early animal development follows fundamentally similar pattern
Remarkable similarity among homeotic genes
- 1 HOM-C cluster in insects
-4 HOX clusters in mammals
paralogous to insect cluster
expressed in segmental fashion in early development
Knockout and genome studies suggest animal development uses same regulatory pathways
Remarkable similarity among homeotic genes: \_\_\_\_\_\_ cluster(s) in insects
1 HOM-C cluster in insects
Remarkable similarity among homeotic genes: \_\_\_\_ cluster(s) in mammals
4 HOX clusters in mammals
Evolutionary conservation of regulatory gene function:
Eyeless/small eye
Flower is organized into 4 concentric rings:
whorl 1: leaflike sepals
whorl 2: petals
whorl 3: stamen (contain pollen)
whorl 4: carpels (fused to stigma bearing ovules)
whorl 1
leaflike sepals
whorl 2
petals
whorl 3
stamen (contain pollen)
whorl 4
carpels
fused to stigma bearing ovules
Sepals
Class A
Carpels
Class C
Petals
Class A & Class B
Stamens
Class B & Class C
