Chapter 1 Flashcards
The information is encoded in DNA in sequences called ____ that code for proteins
genes
Gene expression can be regulated at several levels:
(1)Different genes may be transcribed
(2)DNA transcribed from a gene may be selectively processed to regulate 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.
Genes are contained in a complex of DNA and proteins (mostly histones) called ____
chromatin
Basic unit of structure is the _____
nucleosome
Each nucleosome is composed of an octamer of ______ and approximately 140 base pairs of DNA
histone proteins
Nucleosomes themselves are joined into clusters by binding of DNA existing between nucleosomes (______) with other histone proteins (H1 histones)
(linker DNA)
Inactive state: chromatin appears as beads of nucleosomes on a string of DNA and is referred to as ______
heterochromatin
For transcription to occur, this DNA must be uncoiled from the beads. Uncoiled state, chromatin is referred to as ____
euchromatin
Genes reside within the DNA strand and contain regions called ___, which can be translated into proteins
exons
_____, which are interspersed between exons and which are not transcribed into proteins
Introns
Exons and introns, a typical gene includes the following: a _______ that binds RNA polymerase for the initiation of transcription;
promoter region
Exons and introns, a typical gene includes the following: a promoter region that binds ____ of transcription;
RNA polymerase
Exons and introns, a typical gene includes the following: a promoter region that binds RNA polymerase for the initiation of ____
transcription
The promoter region, where the RNA polymerase binds, usually contains the sequence TATA, and this site is called the ____
TATA box
In order to bind to this site, however, the polymerase requires additional proteins called_____, also have a specific DNA-binding domain plus a transactivating domain that activates or inhibits transcription of the gene whose promoter or enhancer it has bound.
transcription factors
____ are regulatory elements of DNA that activate utilization of promoters to control their efficiency and the rate of transcription from the promoter.
Enhancers
The _____, which participates in pancreas, eye, and neural tube development, contains three separate enhancers, each of which regulates the gene’s expression in the appropriate tissue.
PAX6 transcription factor
Sometimes, enhancers can inhibit transcription and are called ____
silencers
____ of cytosine bases in the promoter regions of genes represses transcription of those genes.
Methylation
one of the X chromosomes in each cell of female is inactivated (_____) by this methylation mechanism.
X chromosome inactivation
_____ is also responsible for genomics imprinting in which only a gene inherited from the father or the mother is expressed, whereas the other gene is silenced.
DNA methylation
DNA methylation is also responsible for _____ in which only a gene inherited from the father or the mother is expressed, whereas the other gene is silenced
genomics imprinting
The initial transcript of a gene is called ___ or sometimes premessenger RNA.
nuclear RNA (nRNA)
The initial transcript of a gene is called nuclear RNA (nRNA) or sometimes _____
premessenger RNA
The process is carried out by _____, which are complexes of small nuclear RNAs (snRNAs) and proteins that recognize specific splice sites at the 5’ or the 3’ ends of the nRNA
spliceosomes
Proteins derived from the same gene are called splicing isoforms (also called _____ or ____), and these afford the opportunity for different cells to use the same gene to make proteins specific for that cell type
splice variants or alternative splice forms
Proteins derived from the same gene are called _____ (also called splice variants or alternative splice forms), and these afford the opportunity for different cells to use the same gene to make proteins specific for that cell type.
splicing isoforms
Most often, one group of cells or tissues causes another set of cells or tissues to change their fate, a process called _____
induction
Even after a protein is made (translated), there may be ______ that affect its function.
post translational modifications
In each such interaction, one cell type or tissue is the inducer that produces a signal, and one is the ____ to that signal
responder
In each such interaction, one cell type or tissue is the _____ that produces a signal, and one is the responder to that signal
inducer
The capacity to respond to such a signal is called competence, and competence requires activation of the responding tissue by a ____
competence factor
The capacity to respond to such a signal is called ____, and competence requires activation of the responding tissue by a competence factor
competence
Many inductive interactions occur between epithelial and mesenchymal cells and are called _____
epithelial—mesenchymal interactions
_____ are joined together in tubes or sheets, whereas mesenchymal cells are fibroblastic in appearance and dispersed in extracellular matrices.
Epithelial cells
Examples of epithelial—mesenchymal interactions include the following:
- ______ and surrounding mesenchyme to produce gut-derived organs, including the liver and pancreas
gut endoderm
Examples of epithelial—mesenchymal interactions include the following:
- gut endoderm and surrounding mesenchyme to produce gut-derived organs, including the _____
liver and pancreas
Examples of epithelial—mesenchymal interactions include the following:
- ____ with overlying ectoderm (epithelium) to produce limb outgrowth and differentiation; and endoderm of the ureteric bud and mesenchyme from the metanephric blastema to produce nephrons in the kidney
limb mesenchyme
Examples of epithelial—mesenchymal interactions include the following:
- limb mesenchyme with overlying ectoderm (epithelium) to produce limb outgrowth and differentiation; and endoderm of the___ and mesenchyme from the metanephric blastema to produce ____ in the kidney
ureteric bud - nephrons
_____ can also occur between two epithelial tissues, such as induction of the lens by the epithelium of the optic cup.
Inductive interactions
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 continue.
crosstalk
______ is essential for induction, for conference of competency to respond, and for crosstalk between inducing and responding cells
Cell-to-cell signaling
These lines of communication are established by:
- ______, whereby proteins synthesized by one cell diffuse over short distances to interact with other cells, or by _____, which do not involve diffusable proteins
Paracrine interactions - juxtacrine interactions
The ______ responsible for paracrine signaling are called paracrine factors or growth and diiferentiation factors (GDFs).
diffusable proteins
The diffusable proteins responsible for paracrine signaling are called____ or growth and diiferentiation factors (GDFs)
paracrine factors
___, Paracrine factors act by signal transduction pathways either by activating a pathway directly or by blocking the activity of an inhibitor of a pathway (inhibiting an inhibitor, as is the case with hedgehog signaling)
Paracrine Signaling
Paracrine Signaling, Paracrine factors act by _____ either by activating a pathway directly or by blocking the activity of an inhibitor of a pathway (inhibiting an inhibitor, as is the case with hedgehog signaling)
signal transduction pathways
_____ include a signaling molecule (the ligand) and a receptor.
Signal transduction pathways
Signal transduction pathways include a signaling molecule (the ligand) and a ___
receptor
Signal transduction pathways include a signaling molecule (the ____) and a receptor
ligand
The receptor spans the cell membrane and has an ____ (the ligand-binding region), a _____, and a ___
extracellular domain - transmembrane domain - cytoplasmic domain
Usually, the result of this activation is to confer enzymatic activity to the receptor, and most often, this activity is a ___that can phosphorylate other proteins using ATP as a substrate
kinase
_____ - Mediated through signal transduction pathways as well but does not involve diffusable factors
Juxtacrine Signaling
In turn, phosphorylation activates these proteins to phosphorylate additional proteins, and thus, a cascade of protein interactions is established that ultimately activates a _____
transcription factor
The ____ represents an example of this type of signaling
Notch pathway
Usually, the result of this activation is to confer enzymatic activity to the receptor, and most often, this activity is a kinase that can __ other proteins using ATP as a substrate
phosphorylate
The extracellular matrix is the milieu in which cells reside. This milieu consists of large molecules secreted by cells including ___, ____ (chondroitin sulfates, hyaluronic acid, etc.), and ___, such as ___ and ____
collagen, proteoglycans - glycoproteins - fibronectin and laminin
For example, laminin and type IV collagen are components of the ____ for epithelial cell attachment, and fibronectin molecules form scaffolds for cell migration
basal lamina
For example, ____ and ____ are components of the basal lamina for epithelial cell attachment, and fibronectin molecules form scaffolds for cell migration
laminin and type IV collagen
Receptors that link extracellular molecules such as fibronectin and laminin to cells are called ____
integrins
These receptors “integrate” matrix molecules with a cell’s_____ (e.g., actin microfilaments), thereby creating the ability to migrate along matrix scaffolding by using contractile proteins, such as actin.
cytoskeletal machinery
There is direct transmission of signals from one cell to another by _____
gap junctions
These receptors “integrate” matrix molecules with a cell’s cytoskeletal machinery (e.g., actin microfilaments), thereby creating the ability to migrate along matrix scaffolding by using contractile proteins, such as ____
actin
The junctions themselves are made of _____ that form a channel, and these channels are “connected” between adjacent cells.
connexin proteins
The four groups of GDFs:
1.fibroblast growth factor (FGF)
2.WNT
3.Hedgehog\
4.Transforming growth factor-B (TGF-B) families
There is a large number of paracrine signaling factors acting as ligands, which are also called ____
GDFs
______ - Originally named because they stimulate the growth of fibroblasts in culture; they can produce hundreds of protein isoforms by altering their RNA splicing or their initiation codons
Fibroblast Growth Factors
FGF proteins produced by these genes activate a collection of tyrosine receptor kinases called _____
fibroblast growth factor receptors (FGFRs)
FGF proteins produced by these genes activate a collection of _____ called fibroblast growth factor receptors (FGFRs)
tyrosine receptor kinases
____ is important for the development of the limbs and parts of the brain
FGF8
______ - The hedgehog gene was named because it coded for a pattern of bristles on the leg of Drosophila that resembled the shape of a hedgehog
Hedgehog Proteins
In mammals, there are 3 hedgehog genes:
1.Desert
2.Indian
3.Sonic hedgehog
_____ - Their receptors are members of the frizzled family of proteins
WNT Proteins
WNT proteins are involved in ____, ____, and some aspects of ____ and ____ differentiation among other actions
regualting limb patterning , midbrain development, somite and urogenita
The TGF-B superfamily has more than 30 members and includes the;
1.TGF-Bs
2.The bone morphogenetic proteins (BMPs)
3.The activin family
4.The müllerian inhibiting factor (MIF, anti-müllerian hormone)
The first member of the family, ___, was isolated from virally transformed cells.
TGF-B members are important for extracellular matrix formation and epithelial branching that occurs in lung, kidney, and salivary gland development.
TGF-B1
The first member of the family, TGF-B1, was isolated from virally transformed cells.
TGF-B members are important for ___ and epithelial branching that occurs in lung, kidney, and salivary gland development.
extracellular matrix formation
The first member of the family, TGF-B1, was isolated from virally transformed cells.
TGF-B members are important for extracellular matrix formation and epithelial branching that occurs in ____, ____, and ___.
lung, kidney, and salivary gland development
Another group of paracrine signaling molecules important during development are neurotransmitters, including;
1.serotonin
2.y-amino butyric acid (GABA)
3.epinephrine
4.norepinephrine
____ acts as a ligand for a large number of receptors, most of which are G protein—coupled receptors, regulates a variety of cellular functions, including cell proliferation and migration, and is important for establishing laterality, gastrulation, heart development, and other processes during early stages of differentiation
Serotonin (5-HT)
____ also acts through receptors and appears to play a role in apoptosis (programmed cell death) in the interdigital spaces and in other cell types
Norepinephrine
the protein ___comes closest to being the master morphogen of them all.
SHH
The protein binds to its receptor _____, normally inhibits the receptor-like protein Smoothened (Smo).
Patched (Ptc)
The protein binds to its receptor Patched (Ptc), a protein that normally inhibits the receptor-like protein ____
Smoothened (Smo)
Upon binding of SHH to Ptc, Ptc activity is eliminated, the inhibition of Smo is removed, and Smo is activated to, ultimately, upregulate activity of the ____ (1 to 3) of transcription factors that control expression of target genes
GLI family
The specificity of SHH expression in different cell types is regulated by _____ acting independently to control SHH transcription in different cells and tissues
multiple enhancer elements
Its release from the plasma membrane is produced by the transmembrane protein ___, and at this point, SHH can establish the concentration gradients characteristic of its action as a morphogen.
Dispatched
The SHH protein has some unique characteristics, including the fact that after translation, it is cleaved and ____ is added to the C-terminus of its N-terminal domain
cholesterol
The _____ regulates the process of convergent extension whereby a tissue becomes longer and narrower
planar cell polarity (PCP) pathway
PCP refers to the reorganization of cells and cell sheets in the plane of a tissue, such as occurs during _____
convergent extension
The principal PCP signaling pathway:
- ______, which includes the Wnt receptor Frizzled (Fz)
- ___ and ___
noncanonical WNT pathway
Celsr and Vangl
These transmembrane proteins primarily target activation of _____, either directly or through downstream effectors, such as Prickle (Pk) and Diego (Dgo)
DISHEVELLED (DVL)
The principal PCP signaling pathway:
- noncanonical WNT pathway, which includes the ______
- Celsr and Vangl
Wnt receptor Frizzled (Fz)
In turn, Dvl regulates signaling via the ____ and ___ N-terminal kinases (JNK) that control cytoskeletal changes and other down- stream eifectors including transcription factors.
Rho and Rac kinases
These transmembrane proteins primarily target activation of DISHEVELLED (DVL), either directly or through downstream effectors, such as ____ and ___
Prickle (Pk) and Diego (Dgo)
In turn, Dvl regulates signaling via the Rho and Rac kinases to upregulate ___ and other down- stream eifectors including transcription factors.
c-Jun N-terminal kinases (JNK)
Notch transmembrane receptors bind to transmembrane ligands of the_____, which requires cell-to-cell contact (juxtacrine signaling) for signaling to occur
DSL (Delta/Serrate/ LAG-2) family
In turn, Dvl regulates signaling via the Rho and Rac kinases to upregulate c-Jun N-terminal kinases (JNK) that control ____ and other down- stream eifectors including transcription factors.
cytoskeletal changes
In mammals, there are four Notch family members and five transmembrane ligands (______)
lagged 1 and 2 and Delta 1 to 3
Binding of one of these proteins to a Notch receptor causes a conformational change in the Notch protein such that part of it on the cytoplasmic side of the membrane is cleaved.
True/False
True
The pathway is very straightforward in that there are no second messengers involved.
True/ False
True
___ have also been linked to cases of tetralogy of Fallot (a cardiac outflow tract defect).
JAG1 mutations
JAG1 mutations have also been linked to cases of _____ (a cardiac outflow tract defect).
tetralogy of Fallot
Mutations in JAG1 or NOTCH2 cause ___ characterized by cardiac outflow tract defects as well as skeletal, ocular, renal, and hepatic abnormalities
Alagille syndrome
