Introduction to Molecular Regulation and Signaling

Question 1

Embryonic development is directed by ______ that contain all of the information required to make an individual. The information is encoded in ______ in sequences called ______ that code for proteins. In turn, proteins regulate expression of other genes and act as signal molecules to orchestrate development.

Answer 1

genomes, DNA, genes

Question 2

There are approximately ______ genes in the human genome, which represents only one-fifth of the number (______) predicted prior to completion of the Human Genome Project. Because of various levels of regulation, however, the number of proteins derived from these genes is closer to the original predicted number of genes. What has been disproved is the ______ hypothesis. Thus, through a variety of mechanisms, a single gene may give rise to many proteins.

Answer 2

23,000, 100,000, one gene—one protein

Question 3

Gene expression can be regulated at several levels:

Answer 3

(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, and
(4) proteins made from the mRNAs may be differentially modified

Question 4

Genes are contained in a complex of DNA and proteins (mostly histones) called ______, and its basic unit of structure is the ______.

Answer 4

chromatin, nucleosome

Question 5

Each nucleosome is composed of an octamer of ______ and approximately ______ base pairs of DNA.

Answer 5

histone proteins, 140

Question 6

Nucleosomes themselves are joined into clusters by binding of DNA existing between nucleosomes (______) with other histone proteins.

Answer 6

linker DNA

Question 7

Nucleosomes keep the DNA tightly coiled, such that it cannot be transcribed. In this inactive state, chromatin appears as beads of nucleosomes on a string of DNA and is referred to as ______. For transcription to occur, this DNA must be uncoiled from the beads. In this uncoiled state, chromatin is referred to as ______.

Answer 7

heterochromatin, euchromatin

Question 8

Genes reside within the DNA strand and contain regions called ______, which can be translated into proteins, and ______, which are interspersed between exons and which are not transcribed into proteins.

Answer 8

exons, introns

Question 9

In addition to exons and introns, a typical gene includes the following: a ______ that binds ______ for the initiation of ______; a ______; a ______ to designate the first amino acid in the protein; a ______; and a ______ untranslated region that includes a sequence (the poly A addition site) that assists with stabilizing the mRNA, allows it to exit the nucleus, and permits it to be translated into protein.

Answer 9

promoter region, RNA polymerase, transcription, transcription initiation site, translation initiation site, translation termination codon, 3’

Question 10

By convention, the ______ and the ______ regions of a gene are specified in relation to the RNA transcribed from the gene.

Answer 10

5’, 3’

Question 11

DNA is transcribed from the ______ to the ______ end, and the ______ is upstream from the transcription initiation site.

Answer 11

5’, 3’, promoter region

Question 12

The ______, where the RNA polymerase binds, usually contains the sequence TATA, and this site is called the ______. In order to bind to this site, however, the polymerase requires additional proteins called ______.

Answer 12

promoter region, TATA box, transcription factors

Question 13

Transcription factors also have a specific ______ plus a ______ that activates or inhibits transcription of the gene whose promoter or enhancer it has bound.

Answer 13

DNA-binding domain, transactivating domain

Question 14

In combination with other proteins, ______ activate gene expression by causing the DNA nucleosome complex to unwind, by releasing the ______ so that it can transcribe the DNA template, and by preventing new ______ from forming.

Answer 14

transcription factors, polymerase, nucleosomes

Question 15

______ are regulatory elements of DNA that activate utilization of promoters to control their efficiency and the rate of transcription from the promoter.

Answer 15

Enhancers

Question 16

Enhancers can reside anywhere along the ______ and do not have to reside close to a ______.

Answer 16

DNA strand, promoter

Question 17

Like promoters, ______ bind transcription factors (through the transcription factor’s transactivating domain) and are used to regulate the timing of a gene’s expression and its cell-specific location. For example, ______ in a gene can be used to direct the same gene to be expressed in different tissues.

Answer 17

enhancers, separate enhancers

Question 18

The ______ transcription factor, which participates in pancreas, eye, and neural tube development, contains ______ separate enhancers, each of which regulates the gene’s expression in the appropriate tissue.

Answer 18

PAX6, three

Question 19

Enhancers act by altering chromatin to expose the ______ or by facilitating binding of the ______.

Answer 19

promoter, RNA polymerase

Question 20

Sometimes, enhancers can inhibit transcription and are called ______. This phenomenon allows a transcription factor to ______ one gene while ______ another by binding to different enhancers.

Answer 20

silencers, activate, silencing

Question 21

______ themselves have a DNA-binding domain specific to a region of DNA plus a transactivating domain that binds to a promoter or an enhancer and activates or inhibits the gene regulated by these elements.

Answer 21

Transcription factors

Question 22

DNA Methylation ______ Transcription

Answer 22

Represses

Question 23

Methylation of cytosine bases in the promoter regions of genes ______ transcription of those genes. Thus, some genes are ______ by this mechanism. For example, one of the X chromosomes in each cell of a female is inactivated (______) by this methylation mechanism. Similarly, genes in different types of cells are ______ by methylation, such that muscle cells make muscle proteins (their promoter DNA is mostly unmethylated) but not blood proteins (their DNA is highly methylated). In this manner, each cell can maintain its characteristic differentiated state.

Answer 23

represses, silenced, X chromosome inactivation, repressed

Question 24

DNA methylation is also responsible for genomic ______ in which only a gene inherited from the father or the mother is expressed, whereas the other gene is silenced.

Answer 24

imprinting

Question 25

Approximately ______ to ______ human genes are imprinted, and their methylation patterns are established during ______ and ______.

Answer 25

40, 60, spermatogenesis, oogenesis

Question 26

Methylation silences DNA by inhibiting binding of ______ or by altering ______ resulting in stabilization of nucleosomes and tightly coiled DNA that cannot be transcribed.

Answer 26

transcription factors, histone binding

Question 27

The initial transcript of a gene is called ______ (______) or sometimes ______.

Answer 27

nuclear RNA, nRNA, premessenger RNA

Question 28

nRNA is ______ than mRNA because it contains introns that are removed (______) as the nRNA moves from the nucleus to the cytoplasm. In fact, this splicing process provides a means for cells to produce different proteins from a single gene. For example, by removing diiferent introns, exons are “spliced” in different patterns, a process called ______.

Answer 28

longer, spliced out, alternative splicing

Question 29

The process (alternative splicing) is carried out by ______, which are complexes of ______ and proteins that recognize specific splice sites at the ______ or the ______ ends of the nRNA.

Answer 29

spliceosomes, small nuclear RNAs (snRNAs), 5’, 3’

Question 30

Proteins derived (alternative splicing) from the same gene are called ______ (also called ______ or ______), and these afford the opportunity for different cells to use the same gene to make proteins specific for that cell type. For example, isoforms of the WT1 gene have different functions in gonadal versus kidney development.

Answer 30

splicing isoforms, splice variants, alternative splice forms

Question 31

Even after a protein is made (translated), there may be ______ that affect its function. For example, some proteins have to be cleaved to become active, or they might have to be phosphorylated. Others need to combine with other proteins or be released from sequestered sites or be targeted to specific cell regions.

Answer 31

posttranslational modifications

Question 32

There are many regulatory levels for ______ and ______ proteins, such that although only 23,000 genes exist, the potential number of proteins that can be synthesized is probably closer to ______ times the number of genes.

Answer 32

synthesizing, activating, five

Question 33

______ are formed by interactions between cells and tissues.

Answer 33

Organs

Question 34

Most often, one group of cells or tissues causes another set of cells or tissues to change their fate, a process called ______. In each such interaction, one cell type or tissue is the ______ that produces a signal, and one is the ______ to that signal.

Answer 34

induction, inducer, responder

Question 35

The capacity to respond to such a signal is called ______, and it requires activation of the responding tissue by a ______.

Answer 35

competence, competence factor

Question 36

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

Answer 36

epithelial—mesenchymal interactions

Question 37

Epithelial cells are joined together in ______ or ______, whereas mesenchymal cells are ______ in appearance and dispersed in ______.

Answer 37

tubes, sheets, fibroblastic, extracellular matrices

Question 38

Examples of epithelial—mesenchymal interactions include the following:

______ and surrounding ______ to produce gut-derived organs, including the liver and pancreas;

______ with overlying ______ to produce limb outgrowth and differentiation;

and ______ and ______ to produce nephrons in the kidney.

Answer 38

gut endoderm, mesenchyme

limb mesenchyme, ectoderm (epithelium)

endoderm of the ureteric bud, mesenchyme from the metanephric blastema

Question 39

______ can also occur between two epithelial tissues, such as induction of the lens by epithelium of the optic cup.

Answer 39

Inductive interactions

Question 40

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.

Answer 40

crosstalk

Question 41

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

Answer 41

Cell-to-cell signaling, paracrine interactions, juxtacrine interactions

Question 42

The diffusable proteins responsible for paracrine signaling are called ______ or ______.

Answer 42

paracrine factors, growth and differentiation factors (GDFs)

Question 43

Signal Transduction Pathways:

Answer 43

Paracrine Signaling
Juxtacrine Signaling

Question 44

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 ______).

Answer 44

signal transduction pathways, hedgehog signaling

Question 45

Paracrine Signaling

Signal transduction pathways include a ______ (the ______) and a ______.

Answer 45

signaling molecule, ligand, receptor

Question 46

Paracrine Signaling

The receptor spans the cell membrane and has an ______ domain (the ______), a ______ domain, and a ______ domain.

Answer 46

extracellular, ligand-binding region, transmembrane, cytoplasmic

Question 47

Paracrine Signaling

When a ligand binds its receptor, it induces a conformational change in the receptor that activates its 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 ______ other proteins using ATP as a substrate. In turn, phosphorylation activates these proteins to phosphorylate additional proteins, and thus, a cascade of protein interactions is established that ultimately activates a ______. This transcription factor then activates or inhibits ______.

Answer 47

kinase, phosphorylate, transcription factor, gene expression

Question 48

Paracrine Signaling

The pathways are numerous and complex and in some cases are characterized by one protein ______ another that in turn ______ another protein (much like the situation with ______).

Answer 48

inhibiting, activates, hedgehog signaling

Question 49

Juxtacrine Signaling

Juxtacrine signaling is mediated through ______ as well but does not involve ______.

Answer 49

signal transduction pathways, diffusable factors

Question 50

Juxtacrine Signaling

There are three ways juxtacrine signaling occurs:

Answer 50

(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 51

Juxtacrine Signaling

(1) A protein on one cell surface interacts with a receptor on an adjacent cell in a process analogous to paracrine signaling.

The ______ represents an example of this type of signaling.

Answer 51

Notch pathway

Question 52

Juxtacrine Signaling

(2) Ligands in the extracellular matrix secreted by one cell interact with their receptors on neighboring cells.

The extracellular matrix is the ______ in which cells reside. This consists of large molecules secreted by cells including ______, ______ (chondroitin sulfates, hyaluronic acid, etc.), and ______, such as fibronectin and laminin. These molecules provide a substrate for cells on which they can anchor or migrate.

Answer 52

milieu, collagen, proteoglycans, glycoproteins

Question 53

Juxtacrine Signaling

(2) Ligands in the extracellular matrix secreted by one cell interact with their receptors on neighboring cells.

For example, laminin and type IV collagen are components of the ______ for epithelial cell attachment, and fibronectin molecules form scaffolds for cell migration. Receptors that link extracellular molecules such as fibronectin and laminin to cells are called ______. 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 ______.

Answer 53

basal lamina, integrins, cytoskeletal machinery, actin

Question 54

Juxtacrine Signaling

(2) Ligands in the extracellular matrix secreted by one cell interact with their receptors on neighboring cells.

Also, ______ can induce gene expression and regulate differentiation as in the case of chondrocytes that must be linked to the matrix to form cartilage.

Answer 54

integrins

Question 55

Juxtacrine Signaling

(3) There is direct transmission of signals from one cell to another by gap junctions.

These junctions occur as channels between cells through which small molecules and ions can pass. Such communication is important in tightly connected cells like epithelia of the ______ and ______ because they allow these cells to act in concert.

Answer 55

gut, neural tube

Question 56

Juxtacrine Signaling

(3) There is direct transmission of signals from one cell to another by gap junctions.

The junctions themselves are made of ______ that form a channel, and these channels are “connected” between adjacent cells.

Answer 56

connexin proteins

Question 57

It is important to note that there is a great amount of ______ built into the process of signal transduction. For example, paracrine signaling molecules often have many family members such that other genes in the family may compensate for the loss of one of their counterparts. Thus, the loss of function of a signaling protein through a gene mutation does not necessarily result in abnormal development or death. In addition, there is cross- talk between pathways, such that they are inti- mately interconnected. These connections provide numerous additional sites to regulate signaling.

Answer 57

redundancy

Question 58

There is a large number of paracrine signaling factors acting as ligands, which are also called ______. Most are grouped into ______ families, and members of these same families are used repeatedly to regulate development and differentiation of organ systems. Furthermore, the same factors regulate organ development throughout the animal kingdom from Drosophila to humans.

Answer 58

GDFs, four

Question 59

The four groups of GDFs include the ______, ______, ______, and ______ families.

Answer 59

fibroblast growth factor (FGF), WNT, hedgehog, transforming growth factor-B (TGF-B)

Question 60

Each family of GDFs interacts with its own family of receptors, and these receptors are as important as the signal molecules themselves in determining the outcome of a ______.

Answer 60

signal

Question 61

Fibroblast Growth Factors

Originally named because they stimulate the growth of fibroblasts in culture, there are now approximately ______ FGF genes that have been identified, and they can produce hundreds of protein isoforms by altering their ______ or their ______. FGF proteins produced by these genes activate a collection of ______ called ______. In turn, these receptors activate various signaling pathways.

Answer 61

two dozen, RNA splicing, initiation codons, tyrosine receptor kinases, fibroblast growth factor receptors (FGFRs)

Question 62

Fibroblast Growth Factors

FGFs are particularly important for ______, ______, and ______. Although there is redundancy in the family, such that FGFs can sometimes substitute for one an- other, individual FGFs may be responsible for specific developmental events.

Answer 62

angiogenesis, axon growth, mesoderm differentiation

Question 63

Fibroblast Growth Factors

For example, ______ is important for development of the limbs and parts of the brain.

Answer 63

FGF8

Question 64

Hedgehog Proteins

The hedgehog gene was named because it coded for a pattern of bristles on the leg of ______ that resembled the shape of a ______.

Answer 64

Drosophila, hedgehog

Question 65

Hedgehog Proteins

In mammals, there are three hedgehog genes: ______, ______, and ______.

Answer 65

desert, Indian, sonic hedgehog

Question 66

Hedgehog Proteins

______ is involved in a multitude of developmental events

Answer 66

Sonic hedgehog (SHH)

Question 67

WNT Proteins

There are at least ______ different WNT genes that are related to the segment polarity gene, ______ in ______. Their receptors are members of the ______ of proteins.

Answer 67

15, wingless, Drosophila, frizzled family

Question 68

WNT Proteins

WNT proteins are involved in regulating ______, ______, and some aspects of ______ and ______ differentiation among other actions.

Answer 68

lim patterning, midbrain development, somite, urogenital

Question 69

The TGF-B Superfamily

The TGF-B superfamily has more than ______ members and includes the ______, the ______, the ______, the ______ (______, ______), and others.

Answer 69

30, TGF-Bs, bone morphogenetic proteins (BMPs), activin family, müllerian inhibiting factor, MIF, anti-müllerian hormone

Question 70

The TGF-B Superfamily

The first member of the family, ______, was isolated from virally transformed cells.

Answer 70

TGF-B1

Question 71

The TGF-B Superfamily

TGF-B members are important for ______ and ______ that occurs in lung, kidney, and salivary gland development.

Answer 71

extracellular matrix formation, epithelial branching

Question 72

The TGF-B Superfamily

The ______ family induces bone formation and is involved in regulating cell division, cell death (apoptosis), and cell migration among other functions.

Answer 72

BMP

Question 73

Another group of paracrine signaling molecules important during development are neurotransmitters, including ______, ______, ______, and ______, that act as ligands and bind to receptors just as proteins do. These molecules are not just transmitters for neurons; they also provide important signals for embryological development.

Answer 73

serotonin, y-amino butyric acid (GABA), epinephrine, norepinephrine

Question 74

______ (______) acts as a ligand for a large number of receptors, most of which are G protein—coupled receptors. Acting through these receptors, this neurotransmitter 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.

Answer 74

Serotonin, 5-HT

Question 75

______ also acts through receptors and appears to play a role in ______ (programmed cell death) in the interdigital spaces and in other cell types.

Answer 75

Norepinephrine, apoptosis

Question 76

______: Master Gene for Embryogenesis

Answer 76

Sonic Hedgehog

Question 77

In the days before molecular biology, embryologists were convinced of the existence of a master signal that directed all of embryonic development. This signal would act as a ______, a secreted molecule that would establish concentration gradients and instruct cells in how to become different tissues and organs. Although we now know that there are a multitude of signaling molecules that coordinately regulate development, the protein ______ comes closest to being the master morphogen of them all.

Answer 77

morphogen, SHH

Question 78

______ - This protein 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 78

SHH

Question 79

SHH

The protein binds to its receptor ______, a protein that normally inhibits the receptor-like protein ______.

Answer 79

Patched (Ptc), Smoothened (Smo)

Question 80

SHH

Upon binding of SHH to Ptc, ______ is eliminated, the ______ is removed, and Smo is activated to, ultimately, upregulate activity of the ______ (1 to 3) of transcription factors that control expression of target genes.

Answer 80

Ptc activity, inhibition of Smo, GLI family

Question 81

SHH

The specificity of SHH expression in different cell types is regulated by multiple enhancer elements acting independently to control ______ in different cells and tissues.

Answer 81

SHH transcription

Question 82

SHH

The SHH protein has some unique characteristics, including the fact that after translation, it is ______ and ______ is added to the ______ of its ______ domain.

Answer 82

cleaved, cholesterol, C-terminus, N-terminal

Question 83

SHH

It is the addition of cholesterol that links SHH to the ______. Then, a ______ is added to the ______ and SHH becomes fully functional. 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.

Answer 83

plasma membrane, palmitic acid moiety, N-terminus, Dispatched

Question 84

The ______ regulates the process of convergent extension whereby a tissue becomes longer and narrower.

Answer 84

planar cell polarity (PCP) pathway

Question 85

The Planar Cell Polarity: Convergent Extension Pathway

For example, during neural tube formation (______), the neural plate ______ and ______ to form the ______ between the neural folds. Similarly, during ______, cells move medially and the embryonic axis elongates.

Answer 85

neurulation, narrows, elongates, neural groove, gastrulation

Question 86

The Planar Cell Polarity: Convergent Extension Pathway

Other examples of convergent extension include ______ of the cardiac outflow tract and movement of the lateral body wall folds toward the ______.

Answer 86

elongation, midline

Question 87

The Planar Cell Polarity: Convergent Extension Pathway

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

Answer 87

Convergent extension

Question 88

The Planar Cell Polarity: Convergent Extension Pathway

PCP refers to the ______ of cells and cell sheets in the plane of a tissue, such as occurs during convergent extension.

Answer 88

reorganization

Question 89

The Planar Cell Polarity: Convergent Extension Pathway

The principal PCP signaling pathway is the noncanonical ______, which includes the Wnt receptor ______ and two other transmembrane proteins called ______ and ______.

Answer 89

WNT pathway, Frizzled (Fz), Celsr, Vangl

Question 90

The Planar Cell Polarity: Convergent Extension Pathway

These transmembrane proteins (Celsr and Vangl) primarily target activation of ______, either directly or through downstream effectors, such as ______ and ______.

Answer 90

DISHEVELLED (DVL), Prickle (Pk), Diego (Dgo)

Question 91

The Planar Cell Polarity: Convergent Extension Pathway

In turn, Dvl regulates signaling via the ______ and ______ kinases to upregulate ______ that control cytoskeletal changes and other downstream effectors including transcription factors. Mutations in many of these genes, including ______, ______, ______, and ______ have been shown to cause ______ in mice and mutations in VANGL genes have been linked to these types of defects in humans.

Answer 91

Rho, Rac, c-Jun N-terminal kinases (JNK), FZ, CELSR, VANGL, DVL, neural tube defects

Question 92

The Notch Pathway

Notch transmembrane receptors bind to trans- membrane ligands of the ______ (______) family, which requires cell-to-cell contact (______) for signaling to occur.

Answer 92

DSL, Delta/Serrate/ LAG-2, juxtacrine signaling

Question 93

The Notch Pathway

In mammals, there are ______ Notch family members and ______ transmembrane ligands (______ and ______). 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 ______. The pathway is very straightforward in that there are no second messengers involved.

Answer 93

four, five, Jagged 1 and 2, Delta 1 to 3, cleaved

Question 94

The Notch Pathway

The cleaved portion of the protein enters the nucleus directly and binds to a DNA-binding protein that normally represses ______ of Notch target genes. Binding of Notch removes the inhibitory activity of the ______ and permits activation of ______.

Answer 94

transcription, repressor, downstream genes

Question 95

______ is involved in cell proliferation, apoptosis, and epithelial to mesenchymal transitions. It is especially important in neuronal differentiation, blood vessel formation and specification (angiogenesis), somite segmentation, pancreatic B-cell development, B- and T-cell differentiation in the immune system, development of inner ear hair cells, and septation of the outflow tract of the heart.

Answer 95

Notch signaling

Question 96

The Notch Pathway

Mutations in JAG1 or NOTCH2 cause ______ characterized by cardiac outflow tract defects as well as skeletal, ocular, renal, and hepatic abnormalities.

Answer 96

Alagille syndrome

Question 97

The Notch Pathway

JAG1 mutations have also been linked to cases of ______ (a cardiac outflow tract defect).

Answer 97

tetralogy of Fallot

Question 98

There are approximately ______ genes in the human ______, but these genes code for approximately ______ proteins.

Answer 98

23,000, genome, 100,000

Question 99

Genes are contained in a complex of DNA and proteins called ______, and its basic unit of structure is the ______.

Answer 99

chromatin, nucleosome

Question 100

Chromatin appears tightly coiled as beads of nucleosomes on a string and is called ______.

Answer 100

heterochromatin

Question 101

For transcription to occur, DNA must be uncoiled from the beads as ______.

Answer 101

euchromatin

Question 102

Genes reside within strands of DNA and contain regions that can be translated into proteins, called ______, and untranslatable regions, called ______.

Answer 102

exons, introns

Question 103

A typical gene also contains a ______ that binds ______ for the initiation of transcription; a ______, to designate the first amino acid in the protein; a ______; and a ______ untranslated region that includes a sequence (the poly A addition site) that assists with stabilization of the mRNA.

Answer 103

promoter region, RNA polymerase, transcription initiation site, translation termination codon, 3’

Question 104

The RNA polymerase binds to the promoter region that usually contains the sequence TATA, the ______. Binding requires additional proteins called ______.

Answer 104

TATA box, transcription factors

Question 105

Methylation of cytosine bases in the promoter region ______ genes and ______ transcription. This process is responsible for ______ whereby the expression of genes on one of the X chromosomes in females is silenced and also for genomic ______ in which either a paternal or a maternal gene’s expression is repressed.

Answer 105

silences, prevents, X chromosome inactivation, imprinting

Question 106

Different proteins can be produced from a single gene by the process of ______ that removes different introns using ______. Proteins derived in this manner are called ______ or ______. Also, proteins may be altered by posttranslational modifications, such as ______ or ______.

Answer 106

alternative splicing, spliceosomes, splicing isoforms, splice variants, phosphorylation, cleavage

Question 107

______ is the process whereby one group of cells or tissues (the ______) causes another group (the ______) to change their fate. The capacity to respond is called ______ and must be conferred by a ______.

Answer 107

Induction, inducer, responder, competence, competence factor

Question 108

Many inductive phenomena involve ______.

Answer 108

epithelial— mesenchymal interactions

Question 109

Signal transduction pathways include a signaling molecule (the ______) and a ______. The ______ usually spans the cell membrane and is activated by binding with its specific ______. Activation usually involves the capacity to phosphorylate other proteins, most often as a ______. This activation establishes a cascade of enzyme activity among proteins that ultimately activates a transcription factor for initiation of gene expression.

Answer 109

ligand, receptor, receptor, ligand, kinase

Question 110

Cell-to-cell signaling may be ______, involving diffusable factors, or ______, involving a variety of nondifl°usable factors.

Answer 110

paracrine, juxtacrine

Question 111

Proteins responsible for paracrine signaling are called ______ or ______.

Answer 111

paracrine factors, GDFs

Question 112

There are four major families of GDFs: ______, ______, ______, and ______.

Answer 112

FGFs, WNTs, hedgehogs, TGF-Bs

Question 113

In addition to proteins, neurotransmitters, such as ______ and ______, also act through paracrine signaling, serving as ligands and binding to receptors to produce specific cellular responses.

Answer 113

serotonin (5-HT), norepinephrine

Question 114

______ factors may include products of the extracellular matrix, ligands bound to a cell’s surface, and direct cell-to-cell communications.

Answer 114

Juxtacrine

Question 115

There are many cell signaling pathways important for development, but two key pathways involve the protein ______ and the noncanonical ______, better known as the ______ that regulates ______.

Answer 115

SHH, WNT pathway, PCP pathway, convergent extension

Question 116

______ is almost a master gene, and when this gene’s protein product binds to its receptor ______, it removes patched’s inhibition of ______. Once activated, smoothened causes upregulation of the ______ family of transcription factors that control downstream signaling by SHH.

Answer 116

SHH, patched, smoothened, GLI

Question 117

______ is a diffusible factor with a cholesterol molecule bound to it, and it serves as a ______ by establishing concentration gradients that regulate cell responses.

Answer 117

SHH, morphogen

Question 118

______ signaling is involved in many developmental events, including establishing the midline and left—right asymmetry and in patterning many different organs.

Answer 118

SHH

Question 119

The ______ regulates movements of cells and sheets of cells in the plane of a tissue, such that the cells intercalate with other cells in such away that the tissue elongates, a process called convergent extension. These types of cell movements are responsible for lengthening the embryo and the neural tube during gastrulation and neurulation, respectively. Several genes are involved in regulating this process, including ______ and its receptor ______, ______, and ______ that code for transmembrane proteins, and ______ that codes for a protein that acts through Rho and Rac kinases to affect the cyto- skeleton and other genes regulating cell move- ments. Mutations in these genes cause neural tube defects in mice, and those involving VANGL have been linked to these defects in humans.

Answer 119

PCP, WNT, FRIZZLED, CELSR, VANGL, DISHEVELLED