Lecture 6 - Development Flashcards

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1
Q

3 Key Events of Animal Development

A
  1. Cell Division
  2. Cell Differentiation (cells become specialized in structure and function)
  3. Morphogenesis (Different kinds of cells are organized into tissues and organs)
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2
Q

When is directionality of the axes determined?

A

Before fertilization even occurs

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3
Q

Structure of Oocyte Before Fertilization

How does it change once fertilization occurs?

A
  • 2 hemispheres (animal, vegetal)

Animal: where nucleus is located
Vegetal: where yolk/nutrients are

Radially symmetrical
Becomes bilateral upon fertilization

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4
Q

What is a Morphogen?

Significance of Gradient:

A

Initial Pattern Formation

Morphogen

  • signaling molecule that can diffuse along an axis, creating a concentration gradient
  • direct differentiation based on their concentration

Egg cell is not homogenous

  • “front” different from “back”
  • as development progresses, cells sense their “position” in the embryo
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5
Q

Where does the initial morphogen come from?

A

Initial morphogen usually provided by mom within the oocyte

  • maternal effect eners
  • set initial polarity across embryo
  • initial gradiant in place before fertilization occurs
  • gets more precise with future rounds of signaling
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6
Q

How does the morphogen establish polarity?

A
  • MATERNAL EFFECT GENES are deposited by mom before oocyte is fertilized
  • after fertilization it is translated inot a protein
  • high conc of protein signal anterior end
  • acts as transcription factor that turns on certain genes involved in anterior development and serves as more specific morphogens
  • different maternal effect genes are localized to posterior end and code for proteins that are highly exressed at posterior end
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7
Q

How do axes develop/arise?

A
  • morphogens establish polarity in the embryo before fertilization happens (maternal effect genes)
  • ex: give animal vegetal poles
  • gives fertilization a context when it happens
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8
Q

How does fertilization affect the axes?

A
  • initially have anterior/posterior (front/back)

- fertilization determines dorsal/ventral (top/bottom)

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9
Q

Fertilization Stimulation of rearrangements in cytoplasm

A
  • sperm binding creates a dorsal-ventral axis
  • cytoplasmic rotation
  • creates an organizational region opposite the site of sperm entry called the gray crescent
  • establishes polarity of zygote
  • molecules within egg are organized with respect to this polarity
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10
Q

Morphogen Shifting Based on Fertilization

Where are the morphogens?

A

Morphogens shift based on where fertilization occurs to “fine tune” axes

  • give polarity that help set the differences between ant/pos, dors/vent
  • fertilizaction fine tunes where they sit in the embryo so that they are oriented in grey crescent
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11
Q

What happens to morphogens as the daughter cells divide?

A
  • they are NOT divided evenly
  • remain in gradients
  • uneven distribution of signaling molecules sets the stage for differentiation into different cell types
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12
Q

Other Extracellular Signaling (besides morphogens)

A
  • neighbor cells help control differentiation
  • secrete chemical signals
  • chemical signals at different concentrations alter gene transcription and ell differentiation
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13
Q

Major developmental stages?

A
  1. fertilization
  2. cleavage
  3. blastula
  4. gastrulation
  5. organogenesis
    - -> nerulation

FCBGO

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14
Q

Fertilization and the grey crescent

A
  • establishes where grey crescent will form
  • opposite sperm entry site
  • will serve as an important organizing region for future dev
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15
Q

Cleavage

what happens during cleavage?

A

Repackages cytoplasm

  • rapid series of cell division
  • because cytoplasm not homogenous, first divisions result in differential distribution of nutrients and cytoplasmic determinants in early embryo
  • during cleaveage - rapid DNA replication and mitosis but no cell growth
  • solid balls of smaller and smaller cells
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16
Q

Blastula

A
  • when cleavage forms a ball with a central fluid-filled avity
  • cavity = blastocoel
  • individual cells = blastomeres
  • in mammals, blastula is called blastocyst
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17
Q

Fate Maps of Blastula

A
  • development is not random
  • due to dist of cytoplasmic and signal components in the cells of blastula, cells undergo patterns of migration and differentiation
  • at this point cells have not differentiated yet
  • still considered embryonic stem cells pluripotent
  • can PREDICT where they will differentiate based on location
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18
Q

Gastrulation

A

How a ball of cells becomes a complex embryo

  • cell movements set up new stem cell contacts
  • sets up signaling cascades
  • initiate differentiation of cells
  • set the stage for the emergence of a body plan
  • develop multiple tissue layers and distinct body axes
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19
Q

Three Germ Layers

A

Ectoderm, Mesoderm, endoder,

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20
Q

Ectoderm gives rise to…

A
  • epidermis of skin and its derivatives (glands, hair follicles)
  • epithelial lining of mouth and rectum
  • cornea and lens of eye
  • nervous system
    adrenal medula
  • toothe enamel
  • epithelium or pineal and pituitary glands
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21
Q

Mesoderm gives rise to…

A
  • notochord
  • skeletal system
  • muscular system
  • muscular layers of stomach, intestine
  • excretory system
  • circulatory system
  • lymphatic system
  • reproductive system
  • dermis of skin
  • lining of body cavity
  • adrenal cortex
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22
Q

Endoderm gives rise to…

A
  • epithelial lining of digestive tract
  • epithelial lining of respiratory system
  • lining of urethra, rinary bladder, and reproductive system
  • liver
  • pancreas
  • thymus
  • thyroid and parathyroid glands
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23
Q

Gastrulation in sea urchin

A
  • cells at vegetal pole begin to invaginate into blastocoel
  • differentiate
  • become endoderm
  • form primitive gut - archenteron
  • mouth forms where archenteron makes contact with overlying ectoderm
  • opening = blastopore –> will become anus
  • other cells break free and move into blastocoel cavity
  • mesenchyme - cells of mesoderm
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24
Q

primitive gut

A

archenteron

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25
Q

gastrulation in frog

beginning

A
  • ampibian blastulas are more than one cell thick
  • sperm is actually idrected to “animal pole” side of the egg
  • certain cells in gray crescent region change their shapes and cell adhesion properties
  • bulge inwards towards blastocoel
  • opening = blastopore
  • as they move inwards dorsal lip forms
26
Q

gastrulation in frog

later part

A
  • involution - sheet of cells moves inwards
  • group of involuting cells becomes endoderm (form primitive gut)
  • another group of cells moves between endoderm and outer layer to form mesoderm
  • cells from animal hemisphere flatten and move toward site of involution
  • archenteron grows displacing blastocoel
  • three germ layers are created (differentiation)
  • differences among the axes now visible
  • chemical differences had been present, but now physiological differences
  • dorsal/ventral, anterior/posterior
27
Q

Blastocoel vs blastopore

A

Blastocoal - Blastula stage

  • ball of cells with fluid in center
  • ffluid in center = blastocoel

blastopore - gastrulation stage

  • blastopore forms
  • invagination at dorsal lip that will become the archenteron and ultimately the gut
  • pore forming into what was previously the blastula
28
Q

Gastrulation and cell differentiation
(Spemann Organizer)

What did Spemann determine?

A

*cells at the two stages were transplanted to a different salamander

  • EARLY GASTRULAS: cells take on identity of region
  • are pluripotent
  • respond to cues of neighbors
    LATE GASTRULAS: differentiationha d occured
  • cells took on fate of their initial region
  • at some point during gastrulation, differentiation had occurred and fates of enbryonic cels had been determined
29
Q

Gastrulation and Grey Crescent

What did Spemann determine?

A

If grey crescent not evenly divided between cells, they will be different

  • half with grey crescent would be normal
  • half without would stay a clump of undifferentiated cells
30
Q

Importance of grey crescent and dorsal lip

A

crucial for organizing embryo formation

31
Q

The spemann organizer

A
  • dorsal lip of blastopore “organizes” the development of the surrounding cells*
  • small region capable of inducing differentiation of surrounding tissues that otherwise would have had different fates
    discovery: took dorsal lip of the blastopore of one salamander and put it in belly area of another gastrula. A complete second embryo formed in the belly area of the original
32
Q

Molecualr mechanisms underlying the spemann organizer

What molecule is important?

A
  • unequal distribution of cytoplasmic components from cleavage
  • transcription factor B-catenin is distributed highly in the cells that correspond to the location of the organizer
  • Initiates organizer activity
  • Without b catenin, gastrulation does not occur
  • if B-catenin is over-expressed in a different region of the embryo, it induces a second axis of embryo formation
  • initiates complex signaling pathways beween transcription factors and growth fators that control gene expression

** B catenin alone would do the same thing as if a spemann organizer were present

33
Q

The primitive streak

A
  • birds and mammals have primitive streak rather than dorsal lip
  • midline ridge tha invaginates
  • cells migrate through it to become endoderm and mesoderm
  • some cells become notochord and organize development similar to Spemann organizer
  • anterior node is equivalent to spemann organizer
34
Q

Primitive streaks and twins

A
  • if blastocyst splits in two - identical twins
  • cells are still pluripotent so can produce two embryos
  • if blastocyst splits partially - conjoined twins
  • multiple or divided primitive streaks
35
Q

Organogenesis

A

development of many organs and organ systems simultaneously and in coordination with one another

36
Q

Neurulation

A
  • initiation of nervous system
  • at the end of gastrulation, mesodermal layer is underneath the ectodermal layer
  • rod of mesodermal tissue –> notochord
    1. structural support for developing embryo
    2. organizing functions (directs overlying ectoderm to become neural ectoderm through signalling molecules)
  • ectodermal tissue overlying the mesoderm folds in upon itseld to create the nervous system
37
Q

Stages of Neurulation

A

*formation of an inner neural tube from an external sheet of cells

  1. thickening of ectoderm overlying the notochord
    - neural plate
  2. edges of neural plate continue to thicken to form ridges
  3. forms middle groove that deepens as folds roll over it
  4. folds converge in midline and fuse, forming a cylinder
    - neural tube

continuous layer of ectoderm over the top

38
Q

From tube to brain

A
  • on anterior end neural tube bulges
  • becomes major divisions of brain
  • rest of tube becomes spinal cord
  • failure of these processes results in various diseases
39
Q

spina bifida

A

failure of neural folds to fuse at the posterior end

40
Q

ancephaly

A

failure of neural folds to fuse at anterior end

41
Q

Body segmentation during neurulation

A
  • as neural tube forms, mesodermal tissues gather along the sides of the notochord
  • form somites
  • seperate, segmented blocks of mesodermal tissue
  • become vertebrae, ribs, muscles of trunks, limbs
  • as development progresses, different segments of the body change and become specialized
42
Q

Morphogens

A

signaling molecules that diffuse along an axis and direct differentiation based on their concentration

  • set the initial anterior-posterior axis in the embryo
  • different concentration gradients of different morphogens activaate release of other morphogens
  • signaling gets more and more precise with each subsequent round of division
43
Q

Significance of Morphogen Patterns

A
  • subsequent patterns of morphogens allow more and more refinement to a particular pattern
  • cells sense their “position” in the embryo
  • a morphogen sets the positional value of a cell by forming a concentration gradient across the developmental field in which the cell resides
  • sense and respond to position based on gradient
  • increasingly refined position
  • positional info guides pattern formation
  • different concentrations of the morphogen cause different effects
  • multiple morphogens provide unique combinations of skills
44
Q

Cascade of Morphogens

A

*morphogens ultimately effect development of specific body regions by turning on the gene transcription

  • one morphogen acts as a transcriptino factor regulating synthesis of other morphogens only in that specific area
  • increasingly specfic responses to different morphogen gradients
  • different morphogens ultimately activate different hox genes in specific regions of embryo
45
Q

Hox genes

A

*make transcription factors that direct development of specific body segments

  • group of related genes that control development of the body segments slong the anterior-posterior axis
  • different embryonic segments express different hox genes

each encodes a transcription factor that determines form and function of each segment

  • one hox txn factor can activate one gene and express a different gene
  • which hox genes are turned on is based on signaling events that preceded it
46
Q

Drosophila Hox Mutation

A
  • leg hox gene mis-xpresssed in head

- head takes on thoracic identity - legs develop in place of antennae

47
Q

Timing of human development

A

9 months

3 trimesters

48
Q

1st trimester

A
  1. rapid cell division and tissue differentiation
    - embryo most sensitive to pathogens that can cause birth defects
  2. implantation
    ~ 6 days after fertilization
    - gastrulation begins
  3. initial development of all major organ systems begins
    - neurulatinon ~day 17-22
    - heart begins to beat during week 4
    - limbs formed by week 8
  4. week 9: embryo now called FETUS
    - cell diff mostly complete
49
Q

2nd trimester

A
  • grows rapidly in weight
  • limbs elongate
  • fingers, toes, facial features become well formed
  • nervous system continues to develop and does so rapidly
  • fetal movements first felt by mother
50
Q

3rd trimester

A
  • continues to grow rapidly
  • at the end internal organs mature
  • digestive system begins to function
  • lover stores glycogen
  • kidneys produce urine
  • brain undergoes cycles of sleep/wake
  • born as soon as last critical organ (lungs) mature
51
Q

Hox genes and their transcription factors

A

hox transcription factors transcribe specific genes that encode specific proteins that dictate development of different structures (legs, antennae, etc)

different segments of embryo have different combinations of proteins that confer their identity

52
Q

Example process of Hox Txn Genes (Arms)

A
  1. specific morphogen turns on txn of hox gene 4
  2. hox 4 protein (a txn factor) is released
  3. hox 4 txn factor induces txn of many genes that regulate dev of arms
  4. proteins that regulate development of arms are synthesized
  5. arms are formed
53
Q

Hox gene - body region

A
  1. hox gene leads to txn of multiple genes that encode proteins that are necessary to make that particualr structure
  2. provides into about body positioning olong ant/pos axis
  3. helps determine cell fate
54
Q

When does implantation happen? what happens then?

A

~ 6 days after fertilization

- gastrulation begins (cleavage and blastula have already happened)

55
Q

When does neurulation begin?

A
  • neurulatinon ~day 17-22
56
Q

When does the heart begin beating?

A
  • heart begins to beat during week 4
57
Q

When are the limbs finished forming?

A
  • limbs formed by week 8
58
Q

When is the baby most susceptible to pathogens that cause birth defects?

A

1st trimester

59
Q

blastocoal vs blastopore

A

Blastocoel - fluid in the center of blastula

Blastopore - pore that forms/invaginates into what was previously the blastula

60
Q

Anterior node

A

Equivalent of spemann organizer in primitive streak of mammals

called hensen’s node in birds

61
Q

Grey crescent vs dorsal lip vs organizer

A

Grey crescent: region that organizes, before involution

Dorsal Lip: Lip - physical point of the involution

Organizer: molecular basis, concept that there is an organizing region