Midterm 1 Flashcards
define haploinsufficiency
- when one functional copy of the gene is NOT enough to provide enough proteins for normal function
define fertilization
- fusion of sperm and egg to form a zygote
define cleavage
- Rapid cell divisions dividing the zygote cytoplasm into many progressively smaller cells called Blastomeres
- NB: no increase in volume
- by the end of cleavage, the blastomeres would have formed a sphere called blastula
what are the main patterns of cleavage?
- Holoblastic: complete cleavage; the entire egg is divided into smaller cells (mammals)
- Meroblastic: only part of the egg is divided and destined to form the embryo and the other part becomes the yolk (source of nutrition) (chicks)
- the yolk rich pole is called the vegetal pole and the embryonic side is called the animal pole
- Centrolecithal: is a form of meroblastic cleavage in which the yolk is in the center of the egg (fruit flies)
define gastrulation
- period of extensive cell rearrangement
- the stage in which the three germ layers form that will interact to form the organs
what are the requirements to meet to make gastrulation happen?
- EMT: epithelial to mesenchymal transition
- different types of cell movement
- formation of germ layers
- formation of the notochord
describe EMT
describe the different types of cell movement
- Invagination
- Involution
- Ingression
- Delamination
- Epibody
How are cells divided during gastrulation?
- ectoderm
- mesoderm
- endoderm
- germ cells
why is the formation of the notochord important?
- The notochord induces the formation of the nervous system
- the notochord forms from the mesoderm
define organogenesis
- resulting cell differentiation from chemical signals exchanged between cells of the germ layers
- ends in the formation of different organs
define the larval stage
A sexually immature organism
in order to become sexually mature, the larva needs to undergo metamorphosis
the adult stage is the shortest stage with the sole purpose of reproduction( life may end after giving birth)
define specification
- when a cell is committed to a given fate but this commitment can be reversed by changing the environment
- refers to a cell’s ability to differentiate in a neutral environment
- to check isolate cell and culture in a basic medium–> cell should differentiate
define cell determination
- The commitment to a given fate is irreversible
- the cell will differentiate to it’s committed fate regardless of its location ( a different part of the embryo or in culture)
define differentiation
- development into a specialized cell type
- At this stage, the cell is overtly a certain type at a biochemical and a functional level
describe the 2 types of specification
- Autonomous speciation: blastomeres acquire determination factors (determinants) from the egg cytoplasm as they divide. Nearby cells usually differentiate into the same thing since they are located next to each other. Even when isolated, the cells divide and become ciliated in time
- Conditional specification: specification comes from signals released from nearby cells. An intact 4-cell embryo from a pluteus larva can be isolated into 4 and produce a full but smaller organism.
describe syncytial specification
syncytium: a cytoplasm containing many nuclei. Cell membranes haven’t formed between nuclei.
* the cells already contain determinants but in this case, determinants can diffuse and influence nearby nuclei
define morphogen
- A long-range signaling molecule that forms a concentration gradient in the embryo and the specification/differentiation of a cell depends on the concentration of the molecule
describe histone tail modifications
- methylation: condense nucleosomes more tightly together blocking access to promoters
- acetylation: loosens nucleosome packing exposing DNA to RNA polymerase II and transcription factors
describe methylation of H3 tails
- methylated lysines on the H3 histone tail can be bound by either Polcyomb- a transcription repressing protein
- OR by trithorax proteins that stimulate transcription
- the binding or polcyomb or trithorax depend on the lysine position on the H3 tails
- methylation of L4,38 and 79 are associated with gene activation
- methylation of L9 and 27 cause repression
describe the central dogma of biology
- transcription of DNA results in a nuclear RNA sequence containing a 5’cap, 3’ polyA tail and untranslated regions
- Nuclear RNA is processed into messenger RNA through the removal of the introns
- The mRNA is translated by ribosomes
- The protein is usually inactive until post-translational modifications are done on it
what are the 3 types of transcription factors? and their domains
- TFs that bind to promoters
- TFs that bind to enhancers
- TFs that link other TFs( promoter TF to enhancer TF)
- DNA binding domain
- trans-activating domain: binds other proteins that act on inactive genes
- protein-protein interaction domain: allows the formation of a complex (linking TF or TF-promoter)
describe DNA modifications
- DNA methylation on cytosines present in a CG repeat causes gene silencing
- prevents TFs from binding an enhancer
what are the 2 important types of DNA methyltransferase and what is their function?
- Dnmt3: a de novo methyltransferase adds a methyl group to the C of CG repeat on a strand that has not been previously methylated
- Dnmt1: adds a methyl group on the complementary strand of a methylated template
describe local cell-cell communication
juxtacrine signaling in which cell communicate through direct contact of the extracellular sides of receptors.
- heterophilic binding occurs when 2 different receptors come together
- homophilic binding: occurs in the case of 2 of the same receptor on different cells come together
- the third case of juxtacrine signaling occurs when a cell receptor interacts with the particles on the extracellular molecule (glycoproteins for example)
describe long-range signaling
- paracrine signaling
- one cell secretes a signaling protein into the environment. only cells expressing the specific receptor will be able to respond to such signal
how do cadherins expressed on the cell surface cause cell adhesion?
- Cadherins are calcium-dependent transmembrane proteins that function to attach cells of the same type together
- Cadherins are anchored in the intracellular domain by association to Catenin-actin
- Calcium binds to the extracellular domain EC2 causing a conformational change in EC1 that allows it to bind another active EC1
describe EMT in terms of cell adhesion
- signals from paracrine signaling stimulate the receptive cell to inhibit expression of E-cadherin
- cell adhesions are then broken
- the free cell is released from the basement membrane
describe the activation of RTK by fibroblast growth factors (FGFs)
- FGF along with heparan sulfate proteoglycans (HSPG)’s binding to RTK leads to dimerization and autophosphorylation of tyrosine on the intracellular domain of RTKs.
- The adaptor protein SOS and GAP recognize Y-p.
- SOS activates GEF( guanine exchange factor)
- GEF activates RAS by changing its GDP to GTP
- RAS-GTP activates Raf ( protein kinase C)
- Raf activates MEK –> ERK
- ERK phosphorylates certain TFs allowing them to alter gene expression
- This pathway is reinforced by the release of calcium ions
- GAP hydrolysis Ras-GTP to Ras-GDP
describe the JAK-STAT pathway
- prolactin (ligand) binding to receptor-JAK2 causes dimerization and phosphorylation of JAK2s and the receptors
- the activated receptor phosphorylates a Y of a STAT protein (STAT5)
- Stat5 dimerizes and move to the nucleus where it can bind DNA
- STAT5 dimer recruits TFs and results in transcription of the casein gene
describe the Hedgehog signal transduction pathway
- the active form of the receptor is a patched protein that inhibits associated smoothened protein
- binding of hedgehog to the receptor causes a CC that removes the patch freeing smoothened
- smoothened inhibits PKA and Slimb
- Ci is not cleaved which allows it to go to the nucleus
- Associate with CBP and cause transcription of a specific gene
describe the vertebrate hedgehog signal transduction pathway
- similar to previous hedgehog signaling pathway
- Ci is Gli here
- when cleaved Ci/Gli act as a repressor
- when whole GLI/Ci act as an activator
describe the canonical Wnt signal transduction pathway
- In the absence of signal, Beta-catenin interacts with a complex of proteins )GSK3, APC, and Axin) that target b-catenin for protein degradation by proteasome ( Ubiquinate it)
- The Wnt protein binds to its receptor ( part of Frizzled family)
- often the receptor is associated with LRP5/6 and Lgr receptors
- The receptor activates disheveled that inhibit GSK3
- B-catenin is thus free to associate with its cofactor (LEF or TCF) in the nucleus and cause gene transcription
describe the noncanonical pathway of wtn
- binding of Wnt to its receptor causes activation of dishevered
- Rho GTPases activated
- change in cytoskeleton induced
- JNK is also activated and leads to Gene expression
In other cases:
- binding of wnt activates a GPCR which ultimately result in calcium release from the SER
describe the SMAD signaling pathway
describe Notch signaling pathway
