Introduction To Molecular Regulation And Signaling

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Answer 1

Embryology

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The process of progressing from a 💡single cell through the period of establishing 💡organ primordia (the 💡first 8 weeks of human development)

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Embryogenesis/ Organogenesis

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Fetal Period

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The study of the embryological origins and causes for 💡birth defects

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Teratology

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They 💡directs embryonic development because they 💡contain all of the information required to make an individual.

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Genomes

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DNA

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They are contained in a complex of DNA and proteins (mostly histones) called 💡chromatín

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GENES

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23, 000 GENES

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One gene-One protein Hypothesis.

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Gene expression can be regulated at several levels:

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(1) Diíferent genes may be transcribed.
(2) DNA transcribed from a gene may be selectively processed to regúlate which RNAs reach the cytoplasm to become messenger RNAs (mRNAs)
(3) mRNAs may be selectively translated.
(4) Proteins made from the mRNAs may be differentially modified.

Question 11

Genes’ 💡basic unit of structure.

They keep the DNA 💡tightly coiled, such that it cannot be transcribed

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Nucleosome

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Component of nucleosome:

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1. Octamer of histone proteins.

2. 140 Base pairs of DNA

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It is a 💡binding of DNA that join nucleosomes themselves into clusters.

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Linker DNA

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💡Darkly stained chromatin that appears as 💡beads of nucleosomes on a string of DNA.

💡Inactive state

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Heterochromatin

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💡Light stained chromatin which indicates it is in 💡active or 💡uncoiled state

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Euchromatin

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It contain 💡DNA sequences that are 💡translated into proteins.

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Exon

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Introns

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Promoter Region

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RNA Polymerase

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Transcription Initiating Site

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They 💡designates the code for the 💡first amino acid in a protein.

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Translation Initiation Site

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Translation Initiation Codon

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3’ Untranslated Region

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It participates in 💡stabilizing the mRNA, allows it to exit the nucleus, and permits translation into a protein.

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Poly A addition site

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DNA is transcribed from the __.

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5’ to the 3’ end

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It is where the 💡RNA polymerase binds, usually contains the sequence 💡TATA.

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PROMOTER REGION

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Answer 27

TATA Box

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They 💡actívate gene expression in combination with other proteins by causing the DNA nucleosome complex to unwind, by releasing the polymerase so that it can transcribe the DNA template, and by 💡preventing new nucleosomes from forming.

Answer 28

Transcription Factors

Question 29

These are 💡regulatory elements of DNA that 💡actívate utilization of promoters to control their 💡efficiency and the rate of transcription from the promoter.

They 💡bind transcription factors and are used to 💡regulate the timing of a gene’s expression and its cell-specific location.

They act by 💡altering chromatin to expose the promoter or by 💡facilitating binding of the RNA polymerase.

Answer 29

ENHANCERS

Question 30

These are enhancers that 💡inhibit transcription.

It allows a transcription factor to actívate one gene while silencing another by binding to different enhancers.

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Silencers

Question 31

It s a process that 💡represses transcription of cytosine bases in the prometer regions of genes.

It is also responsible for 💡genomic imprinting in which only a gene inherited from the father or the mother is expressed, whereas the other gene is silenced.

Answer 31

DNA Methylation

Question 32

Methylation silences DNA by (1)__ or by (2)__ resulting in 💡stabilization of nucleosomes and 💡tightly coiled DNA that cannot be transcribed.

Answer 32

(1) inhibiting binding of transcription factors

(2) altering histone binding

Question 33

It is a 💡initial transcript of a gene.
It is is 💡longer than mRNA because it 💡contains introns that are removed (spliced out) as the nRNA moves from the nucleus to the cytoplasm.

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nuclear RNA (nRNA) premessenger RNA

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It is a process that provides a means for cells to 💡produce different proteins from a 💡single gene.

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Splicing

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It is a process by 💡removing different introns and exons are “spliced” in different patterns

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Alternative splicing

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They carries out splicing process.

They are complexes of 💡small nuclear RNAs (snRNAs) and proteins that 💡recognize specific splice sites at the 💡5’ or the 3’ ends of the nRNA.

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Spliceosomes

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These proteins derived from the same gene and these afford the opportunity for 💡different cells to 💡use the same gene to make proteins specific for that cell type.

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Splicing Isoforms (also called splice variants or alternative splice forms)

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Post-translational modifícations

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It is a process where 💡one group of cells or tissues causes 💡another set of cells or tissues to 💡change their fate.

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Induction

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A cell or tissue that 💡produces a signal during the process of induction.

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Inducer

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A cell or tissue that 💡response to the signal during the process of induction.

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Responder

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It is the 💡capacity to respond to such a signal during the induction process.

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Competence

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Competence requires activation of the responding tissue by a __.

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Competence Factor

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Many inductive interactions occur between epithelial and mesenchymal cells and are called __.

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Epithelial-Mesenchymal Interactions

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Although an initial signal by the inducer to the responder initiates the inductive event, __ between the two tissues or cell types is essential for differentiation to continué

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Crosstalk

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It is essential for induction, for 💡conference of competency to respond, and for 💡crosstalk between inducing and responding cells.

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Cell-to-cell signaling

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They are the diffusable proteins responsible for paracrine signaling.

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Paracrine factors or growth and differentiation factors (GDFs).

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Paracrine factors act by __ either by activating a pathway directly or by blocking the activity of an inhibitor of a pathway.

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Signal Transduction Pathways

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Signal transduction pathways include a (1)__ and a (2)__.

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(1) signaling molecule (the ligand)

(2) receptor

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Three domains of the receptor that spans the cell membrane:

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1. Extracellular domain (the ligand-binding región)
2. Transmembrane domain
3. Cytoplasmic domain.

Question 51

What is the difference of paracrine signaling to juxtacrine signaling?

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Paracrine signaling involves diffusable proteins/ factor while juxtacrine signaling does not. Both are mediated by signal transduction pathways.

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3 ways juxtacrine signaling occurs:

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(1) A protein on one cell surface interacts with a receptor on an adjacent cell in a process analogous to paracrine signaling
(2) Ligands in the extracellular matrix secreted by one cell interact with their receptors on neighboring cells.
(3) There is direct transmission of signals from one cell to another by gap junctions.

Question 53

The extracellular matrix is the milieu in which cells reside which consists of large molecules secreted by cells including:

These molecules provide a substrate for cells on which they can anchor or migrate.

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Collagen
Proteoglycans (chondroítin sulfates, hyaluronic acid, etc.)
Glycoproteins (fibronectin and lamínin)

Question 54

Receptors that link extracellular molecules such as fibronectin and laminin to cells are called?

They can also induce gene expression and regúlate differentiation

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Integrins

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These are the 4 groups of paracrine signaling factors or GDF:

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Fibroblast Growth Factor (FGF)
WNT
Hedgehog
Transforming growth factor beta (TGF-beta)

OTHERS: Neurotransmitters
Serotonin
GABA
Epinephrine 
Norepinephrine

Question 56

These are 💡tyrosine kinase receptors that activate varíous sígnalíng pathways.

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Fibroblast Growth Factor Receptors (FGFRs)

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Fibroblast Growth Factor Receptors (FGFRs)

are particularly important for:

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Angiogenesis
Axon growth
Mesoderm differentiation

Question 58

It is a FGF ímportant for 💡development of the limbs and parts of the braín.

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FGF8

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3 hedgehog genes in mammals:

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Desert
Indian
Sonic Hedgehog

Question 60

These are paracrine signaling factors that are ínvolved in 💡regulatíng límb patterning, 💡midbraín development, and some aspects of 💡somite and urogenital diíferentiation among other actions.

Answer 60

WNT Proteins

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Give examples of TGF-Beta superfamily

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TGF-Bs
Bone Morphogenetic Proteins (BMPs)
Activin Family
Müllerian Inhibiting Factor (MIF, anti-müllerian hormone)

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A paracrine signaling factor that is ímportant for 💡extracellular matrix formation and 💡epithelíal branching that occurs in lung, kidney, and 💡salivary gland development.

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TGF-Beta

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It is paracrine signaling factor that induces 💡bone formation and is involved in regulatíng 💡cell división, 💡cell death (apoptosis), and 💡cell migration among other functions.

Answer 63

Bone Morphogenetic Proteins (BMPs)

Question 64

A neurotransmitter that acts as a 💡ligand for a large number of receptors, most of which are 💡G protein-coupled receptors.

It regulates a variety of cellular functions, íncluding 💡cell proliferation and migration, and is important for establíshing 💡laterality, 💡gastrulatíon, 💡heart development, and other processes during early stages of differentiation.

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Serotonin (5-HT)

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It is a neurotransmitter that play a role in 💡apoptosis (programmed cell death) in the 💡interdigital spaces and in other cell types.

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Norepinephrine

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Master gene for embryogenesis

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Sonic Hedgehog (SHH) Proteins

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It is a secreted molecule that would 💡establish concentration gradients and 💡instruct cells in how to become diíferent tissues and organs.

Answer 67

MORPHOGEN

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It is a paracrine signaling molecule that is involved in development of the vasculature, left-right axis formation, midline, cerebellum, neural patterning, limbs, smooth muscle patterning, heart, gut, pharynx, lungs, pancreas, kidneys, bladder, hair follicles, teeth, thymocytes, inner ear, eyes, and taste buds: a veritable plethora of developmental events.

Answer 68

SHH Protein

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It is a protein receptor for SHH that normally 💡inhibits the receptor-like protein Smoothened (Smo).

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Patched (Ptc)

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It is a receptor-like protein that is activated when SHH bind to Ptc.

Its activation 💡upregulates the GLI transcription factors that bind to DNA and 💡control downstream effector genes in the SHH pathway.

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Smoothened (Smo)

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It is a 💡convergent extension pathway that regulates the process of convergent extensión whereby a 💡tissue becomes longer and narrower

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Planar Cell polarity (PCP) Pathway

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__ requires changes in cell shape together with cell movement and intercalation with other cells

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Convergent extensión

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It refers to the 💡reorganization of cells and cell sheets in the plañe of a tissue, such as occurs during 💡convergent extensión.

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PCP

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It is the principal 💡PCP signaling pathway which includes the 💡Wnt receptor Frizzled (Fz) and two other transmembrane proteins called 💡Celsr and 💡Vangl

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WNT pathway

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These transmembrane proteins primarily target activation of 💡DISHEVELLED (DVL), either directly or through downstream effectors, such as Prickle (Pk) and Diego (Dgo).

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Celsr and Vangl

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It is the receptor for WNT

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Frizzled (Fz)

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It regulates signaling vía the 💡Rho and Rae kinases to upregulate 💡c-Jun N-terminal kinases (JNK) that control 💡cytoskeletal changes and other downstream effectors including transcription factors.

Answer 77

DVL

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Mutation in this gene will cause 💡neural tube defects in 💡humans

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VANGL

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Mutations in these genes will cause 💡neural tube defects in 💡mice.

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FZ, CELSR, VANGL, and DVL

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These receptors bind to transmembrane ligands of the 💡DSL (Delta/Serrate/ LAG-2) family, which requires 💡cell-to-cell contact (juxtacrine signaling) for signaling to occur.

Answer 80

Notch Transmembrane Receptors

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The notch receptor-DSL interaction will activates a 💡proteolytic enzyme that 💡cleaves the Notch protein to produce the activated membrane anchored __.

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Notch extracellular truncation (NEXT)

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It is released when 💡NEXT is cleaved by an intracellular secretase enzyme.

It represents the 💡active signaling portion of the original Notch receptor.

It translocates directly to the nucleus where it binds to transcription repressors and removes their inhibitory activity on downstream target genes of the Notch pathway.

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Notch intracellular domain [NICD]

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Notch signaling is involved in?

Answer 83

Cell proliferation
Apoptosis
Epithelial to mesenchymal transitions
Neuronal differentiation
Blood vessel formation and specification (angiogenesis)
Somite segmentation
Pancreatic Beta cell development
B- and T-cell differentiation in the immune system
Development of inner ear hair cells
Septation of the outflow tract of the heart.

Question 84

It is caused by the mutations in 💡JAGl or NOTCH2 which is characterized by 💡cardiac outflow tract defects as well as skeletal, ocular, renal, and hepatic abnormalities.

Answer 84

Alagille syndrome