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Embrology > History of embryology > Flashcards

History of embryology Flashcards

1
Q

Before we know how things work

A

We need to know how things became

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2
Q

Physiology begins prior to

A

Completion of anatomical development

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3
Q

“Experimental embryology or developmental biology must stay focused on the

A

“Why” questions and not just on the “How” questions”

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4
Q

Aristotle

A

First used the terms, Zygote for a fertilized egg and Vital Heat to describe the fluids from each parent which mixed to form the offspring.
Aristotle described the two models of development known as:
1) Preformation – Organs are present in miniature form within the gametes, either the egg or sperm.
2) Epigenesis – Organs form “de novo”, or from scratch.

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5
Q

Preformationist

A

crowd used the term “Homunculus” which is a miniature complete human with all organs and body parts already formed and compacted into the sperm or egg. After “fertilization” the homunculus unfolded and proceeded to grow.

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6
Q

Epigenesis

A

is what we now know to be the method of development of the human following fertilization and is the theory that Aristotle also believed in. As the microscope and staining techniques were refined where the embryologist could see the microscopic events in the cells, the Preformation theory was finally disproven.

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7
Q

First Challenges to the Early Embryologist: You don’t have to give specific answers to these questions, just know that they were questions which these early embryologist faced.

A

1) Differentiation – How did a single cell zygote develop to a multi-cellular organism?
2) Morphogenesis – The formation of tissues and organs from various cell types.
3) Growth – How does an organism regulate its cell growth?
4) Reproduction – What is different in the genetic code of the gametes to form new offspring?
5) Evolution – How do organisms alter the formation of structures to meet adaptation needs?
6) Environmental Stresses – Factors which can alter morphogenesis

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8
Q

Karl Ernst von Baer & Christian Pander

A

First observed the Primary Germ Layers in the chicken embryo species and that the germ layers (ectoderm, mesoderm, endoderm) give rise to specific organ systems.

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9
Q

Cellular Basis of Morphogenesis

A

The two (2) primary cell types from which other cells, tissues and organs develop are; 1) Epithelial Cells 2) Messenchymal (stem) Cells

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10
Q

Teratogens

A

Agents which lead to disruptions at the gene level and cause abnormalities and malformations to the developing embryo and fetus.

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11
Q

Embryology

A

The anatomical changes that occur during development from conception to birth.

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12
Q

Development

A

The physiological and molecular events that occur during growth and differentiation of the embryo.

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13
Q

Differentiation

A

How one cell becomes many different kinds of cell types and how DNA segments are switched on and off.

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14
Q

Morphogenesis

A

How differentiated cells become organized into tissues and organs

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15
Q

Apoptosis

A

Programmed cell death. Generally a normal event in the refinement of body parts by removing excess tissue.

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16
Q

Stages of Embryonic Development:

A

1) Cleavage – Creation of the Morula. Zygote starts to divide (cleavage) forming Blastomeres (single
cells).
* Blastomeres all look alike in morphology but not necessarily the same size. Each blastomere
contains the full complement of genetic information therefore each blastomere is diploid.
2) Blastulation – Creation of the Blastula.
3) Gastrulation – Creation of the Gastrula. Beginnings of the 3 germ layers which form the organs and
body structures.
4) Neurulation – Creation of the key parts of the nervous system.
5) Organogenesis – Creation of organs.

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17
Q

Morula

A

As the result of cleavage at approximately 3-4 days after fertilization the embryo is comprised
of 12+ blastomeres. The embryo is in the Morula stage just as the embryo is entering the
uterus.

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18
Q

Blastula (Blastocyst)

A

pproximately 5 days after fertilization (in humans) a fluid filled center forms in the embryo termed the Blastocoel. This results in the Inner Cell Mass (ICM) and an outer ring of blastomeres termed the Trophoblast.

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19
Q

Inner Cell Mass (ICM)

A

Mass of blastomeres that forms at one pole of the blastula. The ICM is also known as the Embryonic Stem Cells and will form all of the body structures of the new offspring.

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20
Q

Trophoblast

A

Blastomeres which form the membranes and structures outside the embryo such as the placenta, allantois, chorion etc.

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21
Q

Embryo

A

The human baby during the first 8 weeks of gestation. Most susceptible time for teratogenic and congenital anomalies to occur.

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22
Q

Fetus

A

The human baby from the 9th week of gestation until birth of the child.

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23
Q

Control of Embryonic Development:

A

Required a coordinated interaction of genetic & environmental factors, and Mechanisms to Guide;

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24
Q

Control of Embryonic Development:

A

1) Differentiation – Stem cells into specific committed cell types
2) Synchronized development – Development of multiple cells, tissues and organs
3) Tissue interaction
4) Migration of Cells – Movement of like/similar cells towards each other to form tissues
5) Controlled proliferation – To prevent excess cell numbers and possibly tumor formation
6) Programmed cell death - Apoptosis, to remove excess and unnecessary cells/tissues

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25
Q

Cell-Cell Interactions; Terminology

A

1) Inducer - Cells producing chemical signal affecting the development of other cells
2) Responder – Cells which receive inducing signal
3) Competence – Ability of cells to respond
4) Reciprocity – Induction of the inducer cells

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26
Q

Interactions Between Inducer and Responder:

A

Instructive Interaction - Initiation of gene expression from scratch which leads to differentiation
Permissive Interaction – Responder is already specified but just requires the proper environment to
develop
- Gene Expression can only go as far as that the responder already holds within it’s genotype.

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27
Q

Inducer Molecules:

A

1) Paracrine Factors – Soluble proteins which diffuse over a short distance. No physical contact is
required between the inducer and responder cells. Examples – Growth Factors
2) Juxtacrine Factors - Physical interaction between one cell with cell surface receptors of neighbor
cells. Cells are Juxtaposed.
3) Autocrine Factors – Cells respond to their own paracrine factors.
- Any of these Factor types must bind to specific receptors to activate G-proteins.
“Phosphorylation” is the key to altering the activity of competent cells.

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28
Q

2 Examples of Intercellular Pathways:

A

1) RAS-G-protein Pathway – Mutations in this pathway result in the activation of oncogenes and
potential cancer formation.
2) JAK-STAT Pathway – Mutations lead to dwarfism and deficiency in specific blood cell types.

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29
Q

Apoptosis

A

Programmed cell death which may be a normal process in development of the embryo. Growth Factors such as platelet derived growth factors (PDGF) and erythropoietin prevent cells from undergoing apoptosis.

30
Q

Juxtacrine Signaling

A

Utilize a “Notch Pathway” or physical interaction between adjacent cells for
induction. Activate “histone acetyltransferases” for gene expression and are commonly found in the
Nervous System.

31
Q

Extracellular Matrix:
Similar cell to tissue formation, migration and adhesion, is dependent on basement membrane or extracellular matrix attachment sites.
Matrix is comprised of;

A

1) Collagen fibers – for strength and a firm foundation
2) Proteoglycans – Aid in delivery of paracrine factors to cellular receptor sites
3) Fibronectin – Adhesion molecules
4) Integrins – Proteins to bind and unite the extracellular matrix to the intracellular network of actin
filaments.
5) Cadherins – Calcium adhesion molecules
6) Catenins – Actin binding proteins which anchor cadherins intracellularly
- Deficiency in Calcium or Cadherin synthesis leads to embryonic abnormalities.

32
Q

Connexins

A

6 protein units to form a pore between joining cell cytoplasms.

33
Q

Maintenance of Differentiation:

A
  • Maintenance of phenotype through gene expression
  • Autocrine factors produced by the same cell to induce its own expression.
  • Acetylation – Keeps the gene segment accessible.
  • Reciprocal Induction by neighboring cells.
34
Q

Environmental Determinants on Developmental Biology

A
  • Adaptation to environments relates to survival of the embryo
  • Phenotypic Plasticity or Morphs – Alterations Phenotypically
  • Temperature alterations influences sex typing in amphibians
  • UV Irradiation may result in decreased fertilization and survival rates
    “Mycosporin” – Melanin type protection. Lack of Mycosporin may lead to developmental anomalies
35
Q

Cell Specification:

A
  • From single cell zygote to multi-specialized embryo
  • Differentiation – Development of specialized cell types
  • Commitment – Overt biochemical changes to determine a cells fate
36
Q

2 Stage of Commitment:

A

1) Specification – Cell can differentiate “autonomously” in vitro. Reversible commitment.
2) Determination – Cell can go through specification “autonomously” in vivo. Irreversible commitment.

37
Q

Type of Specification:

A

1) Autonomous Specification – Invertebrates. Cells removed from the “blastomere” develop” as normal.
Embryo will lose those structures normally produced by the removed cell types.
“Mosaic Development” – Patchwork, self-differentiating cells.
2) Syncytial Specification – Insects. The nuclei divides within the egg and spreads the information or
nuclear code for each developing part throughout the embryo by means of protein concentrations
referred to as Morphogens.
3) Conditional Specification – Vertebrates including Humans. First forming blastomeres have the ability
to differentiate into various cell types. Interactions of neighboring cells direct the determination of
specific cell types.
“Regulation” – Ability of blastomeres to compensate for missing pieces or cell types.

38
Q

August Weismann

A

Stated that heritable information is carried only in the gametes and not in the somatic cells - Proposed the “Weismann Barrier” which is that heritable information cannot pass to the somatic cells from the gametes. His work as a Preformationist inadvertently solidified the Germ Plasm Theory and Epigenesis.

39
Q

Experimental Approaches to Germ Plasm Theory:

A

1) Defect Experiment – Specific sacrificed portion of the embryo to observe phenotypic affect.
2) Isolation Experiment – Remove a portion of the embryo to observe expression of the embryo and the
removed section.
3) Recombination Experiment – Exchange different regions of the same embryo.
4) Transplantation Experiment – Exchange regions from different embryos.

40
Q

Stem Cells:
Undifferentiated cells that can differentiate in specialized cells and then divide indefinitely through mitosis. Found in multicellular organisms.

A

1) Totipotent Stem Cells – Can differentiate into embryonic body parts and extraembryonic cell types
from the uniting of an egg and sperm cell.
2) Pluripotent Stem Cells – Grow into all of the different cells of the embryonic body. Isolated from the
Inner Cell Mass (ICM) during the blastocyst stage. Also termed the “Embryonic Stem Cells”.
3) Multipotent Stem Cells – The most limited in their ability to differentiate. Examples include the
neuronal stem cells and the hematopoietic stem cells to form differentiate into various blood cell types.

41
Q

The “Geneticist Group” and the “Embryologist”

A

had differing opinions on what was responsible for differentiation of cell types and development of the embryo.

42
Q

Geneticist Evidence:

A

Polyspermic Fertilization – More than one sperm fertilizing the egg cytoplasm resulting in an excess of genetic material, abnormal blastomere formation, embryonic anomalies and a lethal condition to the embryo.

43
Q

Developmental Genetics”

A

Mutated segments of the mouse genome led to abnormal development of embryos. Therefore evidence of genetic control of early stem cell commitment
Eggs with the original nucleus removed failed to develop embryos.

44
Q

The Embryological Theory:

A

The differentiation of cell types was dictated through biochemical changes within the cytoplasm.
We’ve already seen where paracrine and juxtracrine induction factors (i.e. biochemical) were necessary for cell specification and commitment.

Therefore, Both Genetics and Biochemical products are necessary for development of the embryo!

45
Q

“Somatic Nuclear Transfer” – “Cloning”

A

Donor cell nuclei from non-gametes directed the development of a normal “Totipotent” embryo when transferred into the cytoplasm of enucleated eggs.

46
Q

Temporal Effects of Nuclear Transfer:

A

Success of embryo development is dependent upon the “timing” of the transfer. Early blastula stage led to complete differentiation of cell types. Later stages lost potency as cells where already committed prior to transfer.

47
Q

Dolly was identical genotype

A

but not by phenotype to the donor nucleus.

48
Q

Lab Assays to Express, Identify And Work With DNA Segments:

A

1) Polymerase Chain Reaction - Cloning of mass quantities of DNA using reverse transcriptase to create
mRNA and cDNA libraries. The advantage is that no host cell is required. The disadvantage is that
only a single gene can be expressed during one assay procedure
2) Microarrays & Macroarrays – Ability to observe thousands of genes being expressed simultaneously.

49
Q

DNA Insertion Techniques:

A

1) Microinjection – Cloned DNA segments may isolated and modified then physically injected into the
nucleus of fertilized eggs.
2) Transfection – Allow isolated DNA fragments to be absorbed into the cell and incorporated into the
chromosome.
3) Electroporation – Electrical impulses force the DNA fragments into the cells.
4) Vectors – Plasmids and viral phages inject the genetic material into the host genome.

50
Q

Gene Products” – Humans contain ~ 25,000 protein encoding genes therefore at what steps may the regulation occur for the “selective expression” of gene products?

A

1) Differential Gene Transcription – which genes are allowed to be transcribed within the nucleus
2) Selective Nuclear RNA (pre-mRNA) Processing – which transcribed RNA sequences will make it to the cytoplasm
3) Selective mRNA Translation – which mRNA is translated into proteins
4) Differential Protein Modification – the determination of which proteins are activated or made functional

51
Q
  • Chromatin
A

A form of DNA unique to Eukaryotic cells and not found in Prokaryotic cells.

52
Q
  • Nucleosomes
A

the basic units of chromatin which contains the genetic information.
Nucleosome structure is comprised of “histone subunits” which are encased with two
bands of approximately 147 DNA nucleotide base pairs.

53
Q
  • Linker Proteins
A

Approximately 60-80 DNA base pairs which link adjacent nucleosomes

54
Q

Histone-H1

A

is the primary type of histone bound to the linker section.

  • Adjacent nucleosomes which are tightly bound together prevent their uncoiling, a process necessary for the binding of polymerase enzymes and therefore allowing for transcription to occur
  • In this process, histones (H1) repress or regulate the transcription of DNA to mRNA
55
Q

“Acetylation”

A

of the histones promotes the uncoiling of the nucleosomes and DNA allowing for
transcription to occur.

56
Q
  • “Methylation”
A

represses or prevents the uncoiling of the nucleosome units.

57
Q
  • Exons
A

regions of the DNA which code for a protein

58
Q
  • Introns
A

regions of the DNA not expressed in the final amino acid sequence of a protein

59
Q
  • Promoter Site
A

binding location for RNA polymerase enzymes on DNA for transcription of DNA to mRNA

  • A “cap sequence” of 7-methylguanisine and a “tail sequence” of poly-adenine nucleotides are added to the mRNA strand as modification prior to its exiting the nuclear region.
60
Q
  • Enhancers
A

DNA sequence which controls the efficiency and rate of transcription from a specific promoter region of the DNA. There are different enhancers for the transcription of various gene product

61
Q

“Negative Enhancers”

A

are those which repress transcription “temporally” to prevent premature formation of specific proteins and cell types. They can maintain the proper sequence of morphogenesis and organogenesis

62
Q
  • Transcription Factors
A

bind to the enhancer or promoter regions to activate or repress transcription or a particular gene. Recruit acetyl transferases to loosen the histones and nucleosomes for transcription to occur.

63
Q
  • The inner cell mass (ICM) of totipotent stem cells have NOT undergone “methylation” which is why they are still capable of potentially forming all cell types.
A
64
Q
  • Differential RNA Processing or Splicing
A

following transcription, which RNA will be further processed through translation into specific proteins?

65
Q

Censorship

A

different cell types are represented by the processing of specific nuclear RNA
transcripts into specific mRNA.

66
Q

Differential splicing

A

is the assortment of various combinations of “exons”. Different exons produce
different mRNA and consequently different proteins.

67
Q
  • Therefore due to differential splicing there is the case of;
    One Gene producing Multiple Polypeptides or Proteins in Humans
    where in prokaryotic or lower life forms;
    One Gene = One Polypeptide (protein)
  • Due to the scenario above, a mutation in a single gene segment may potentially lead to abnormalities
    or defects in the synthesis of multiple proteins.
A
68
Q
  • Spliceosomes
A

modified form of RNA which binds to nuclear RNA (nRNA) strand and is capable of excising the mutated segment so that transcription and translation may proceed normally.

69
Q
  • Control at The Translation Level
A

the “poly-adenine tail” protects the mRNA from rapid enzymatic degradation in the cytoplasm. This maintenance and stabilization of the mRNA allows for more efficient synthesis of its protein product. mRNA missing the tail (& cap) would be degraded before translation could occur at the ribosomes.

70
Q
  • Following translation, the polypeptide must still go through a series of conformational changes before becoming an active protein product.
A

Embrology (3 decks)

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