Introduction to Molecular Regulation and Signaling Flashcards
1
Q
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.
A
genomes, DNA, genes
2
Q
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.
A
23,000, 100,000, one gene—one protein
3
Q
Gene expression can be regulated at several levels:
A
(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
4
Q
Genes are contained in a complex of DNA and proteins (mostly histones) called ______, and its basic unit of structure is the ______.
A
chromatin, nucleosome
5
Q
Each nucleosome is composed of an octamer of ______ and approximately ______ base pairs of DNA.
A
histone proteins, 140
6
Q
Nucleosomes themselves are joined into clusters by binding of DNA existing between nucleosomes (______) with other histone proteins.
A
linker DNA
7
Q
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 ______.
A
heterochromatin, euchromatin
8
Q
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.
A
exons, introns
9
Q
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.
A
promoter region, RNA polymerase, transcription, transcription initiation site, translation initiation site, translation termination codon, 3’
10
Q
By convention, the ______ and the ______ regions of a gene are specified in relation to the RNA transcribed from the gene.
A
5’, 3’
11
Q
DNA is transcribed from the ______ to the ______ end, and the ______ is upstream from the transcription initiation site.
A
5’, 3’, promoter region
12
Q
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 ______.
A
promoter region, TATA box, transcription factors
13
Q
Transcription factors also have a specific ______ plus a ______ that activates or inhibits transcription of the gene whose promoter or enhancer it has bound.
A
DNA-binding domain, transactivating domain
14
Q
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.
A
transcription factors, polymerase, nucleosomes
15
Q
______ are regulatory elements of DNA that activate utilization of promoters to control their efficiency and the rate of transcription from the promoter.
A
Enhancers
16
Q
Enhancers can reside anywhere along the ______ and do not have to reside close to a ______.
A
DNA strand, promoter
17
Q
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.
A
enhancers, separate enhancers
18
Q
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.
A
PAX6, three
19
Q
Enhancers act by altering chromatin to expose the ______ or by facilitating binding of the ______.
A
promoter, RNA polymerase
20
Q
Sometimes, enhancers can inhibit transcription and are called ______. This phenomenon allows a transcription factor to ______ one gene while ______ another by binding to different enhancers.
A
silencers, activate, silencing
21
Q
______ 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.
A
Transcription factors
22
Q
DNA Methylation ______ Transcription
A
Represses
23
Q
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.
A
represses, silenced, X chromosome inactivation, repressed
24
Q
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.
A
imprinting
25
Approximately ______ to ______ human genes are imprinted, and their methylation patterns are established during ______ and ______.
40, 60, spermatogenesis, oogenesis
26
Methylation silences DNA by inhibiting binding of ______ or by altering ______ resulting in stabilization of nucleosomes and tightly coiled DNA that cannot be transcribed.
transcription factors, histone binding
27
The initial transcript of a gene is called ______ (______) or sometimes ______.
nuclear RNA, nRNA, premessenger RNA
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 ______.
longer, spliced out, alternative splicing
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.
spliceosomes, small nuclear RNAs (snRNAs), 5’, 3’
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.
splicing isoforms, splice variants, alternative splice forms
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.
posttranslational modifications
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.
synthesizing, activating, five
33
______ are formed by interactions between cells and tissues.
Organs
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.
induction, inducer, responder
35
The capacity to respond to such a signal is called ______, and it requires activation of the responding tissue by a ______.
competence, competence factor
36
Many inductive interactions occur between epithelial and mesenchymal cells and are called ______.
epithelial—mesenchymal interactions
37
Epithelial cells are joined together in ______ or ______, whereas mesenchymal cells are ______ in appearance and dispersed in ______.
tubes, sheets, fibroblastic, extracellular matrices
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.
gut endoderm, mesenchyme
limb mesenchyme, ectoderm (epithelium)
endoderm of the ureteric bud, mesenchyme from the metanephric blastema
39
______ can also occur between two epithelial tissues, such as induction of the lens by epithelium of the optic cup.
Inductive interactions
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.
crosstalk
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.
Cell-to-cell signaling, paracrine interactions, juxtacrine interactions
42
The diffusable proteins responsible for paracrine signaling are called ______ or ______.
paracrine factors, growth and differentiation factors (GDFs)
43
Signal Transduction Pathways:
Paracrine Signaling
Juxtacrine Signaling
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 ______).
signal transduction pathways, hedgehog signaling
45
Paracrine Signaling
Signal transduction pathways include a ______ (the ______) and a ______.
signaling molecule, ligand, receptor
46
Paracrine Signaling
The receptor spans the cell membrane and has an ______ domain (the ______), a ______ domain, and a ______ domain.
extracellular, ligand-binding region, transmembrane, cytoplasmic
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 ______.
kinase, phosphorylate, transcription factor, gene expression
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 ______).
inhibiting, activates, hedgehog signaling
49
Juxtacrine Signaling
Juxtacrine signaling is mediated through ______ as well but does not involve ______.
signal transduction pathways, diffusable factors
50
Juxtacrine Signaling
There are three ways juxtacrine signaling occurs:
(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.
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.
Notch pathway
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.
milieu, collagen, proteoglycans, glycoproteins
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 ______.
basal lamina, integrins, cytoskeletal machinery, actin
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.
integrins
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.
gut, neural tube
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.
connexin proteins
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.
redundancy
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.
GDFs, four
59
The four groups of GDFs include the ______, ______, ______, and ______ families.
fibroblast growth factor (FGF), WNT, hedgehog, transforming growth factor-B (TGF-B)
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 ______.
signal
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.
two dozen, RNA splicing, initiation codons, tyrosine receptor kinases, fibroblast growth factor receptors (FGFRs)
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.
angiogenesis, axon growth, mesoderm differentiation
63
Fibroblast Growth Factors
For example, ______ is important for development of the limbs and parts of the brain.
FGF8
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 ______.
Drosophila, hedgehog
65
Hedgehog Proteins
In mammals, there are three hedgehog genes: ______, ______, and ______.
desert, Indian, sonic hedgehog
66
Hedgehog Proteins
______ is involved in a multitude of developmental events
Sonic hedgehog (SHH)
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.
15, wingless, Drosophila, frizzled family
68
WNT Proteins
WNT proteins are involved in regulating ______, ______, and some aspects of ______ and ______ differentiation among other actions.
lim patterning, midbrain development, somite, urogenital
69
The TGF-B Superfamily
The TGF-B superfamily has more than ______ members and includes the ______, the ______, the ______, the ______ (______, ______), and others.
30, TGF-Bs, bone morphogenetic proteins (BMPs), activin family, müllerian inhibiting factor, MIF, anti-müllerian hormone
70
The TGF-B Superfamily
The first member of the family, ______, was isolated from virally transformed cells.
TGF-B1
71
The TGF-B Superfamily
TGF-B members are important for ______ and ______ that occurs in lung, kidney, and salivary gland development.
extracellular matrix formation, epithelial branching
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.
BMP
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.
serotonin, y-amino butyric acid (GABA), epinephrine, norepinephrine
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.
Serotonin, 5-HT
75
______ also acts through receptors and appears to play a role in ______ (programmed cell death) in the interdigital spaces and in other cell types.
Norepinephrine, apoptosis
76
______: Master Gene for Embryogenesis
Sonic Hedgehog
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.
morphogen, SHH
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.
SHH
79
SHH
The protein binds to its receptor ______, a protein that normally inhibits the receptor-like protein ______.
Patched (Ptc), Smoothened (Smo)
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.
Ptc activity, inhibition of Smo, GLI family
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.
SHH transcription
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.
cleaved, cholesterol, C-terminus, N-terminal
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.
plasma membrane, palmitic acid moiety, N-terminus, Dispatched
84
The ______ regulates the process of convergent extension whereby a tissue becomes longer and narrower.
planar cell polarity (PCP) pathway
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.
neurulation, narrows, elongates, neural groove, gastrulation
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 ______.
elongation, midline
87
The Planar Cell Polarity: Convergent Extension Pathway
______ requires changes in cell shape together with cell movement and intercalation with other cells.
Convergent extension
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.
reorganization
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 ______.
WNT pathway, Frizzled (Fz), Celsr, Vangl
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 ______.
DISHEVELLED (DVL), Prickle (Pk), Diego (Dgo)
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.
Rho, Rac, c-Jun N-terminal kinases (JNK), FZ, CELSR, VANGL, DVL, neural tube defects
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.
DSL, Delta/Serrate/ LAG-2, juxtacrine signaling
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.
four, five, Jagged 1 and 2, Delta 1 to 3, cleaved
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 ______.
transcription, repressor, downstream genes
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.
Notch signaling
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.
Alagille syndrome
97
The Notch Pathway
JAG1 mutations have also been linked to cases of ______ (a cardiac outflow tract defect).
tetralogy of Fallot
98
There are approximately ______ genes in the human ______, but these genes code for approximately ______ proteins.
23,000, genome, 100,000
99
Genes are contained in a complex of DNA and proteins called ______, and its basic unit of structure is the ______.
chromatin, nucleosome
100
Chromatin appears tightly coiled as beads of nucleosomes on a string and is called ______.
heterochromatin
101
For transcription to occur, DNA must be uncoiled from the beads as ______.
euchromatin
102
Genes reside within strands of DNA and contain regions that can be translated into proteins, called ______, and untranslatable regions, called ______.
exons, introns
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.
promoter region, RNA polymerase, transcription initiation site, translation termination codon, 3’
104
The RNA polymerase binds to the promoter region that usually contains the sequence TATA, the ______. Binding requires additional proteins called ______.
TATA box, transcription factors
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.
silences, prevents, X chromosome inactivation, imprinting
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 ______.
alternative splicing, spliceosomes, splicing isoforms, splice variants, phosphorylation, cleavage
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 ______.
Induction, inducer, responder, competence, competence factor
108
Many inductive phenomena involve ______.
epithelial— mesenchymal interactions
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.
ligand, receptor, receptor, ligand, kinase
110
Cell-to-cell signaling may be ______, involving diffusable factors, or ______, involving a variety of nondifl°usable factors.
paracrine, juxtacrine
111
Proteins responsible for paracrine signaling are called ______ or ______.
paracrine factors, GDFs
112
There are four major families of GDFs: ______, ______, ______, and ______.
FGFs, WNTs, hedgehogs, TGF-Bs
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.
serotonin (5-HT), norepinephrine
114
______ factors may include products of the extracellular matrix, ligands bound to a cell’s surface, and direct cell-to-cell communications.
Juxtacrine
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 ______.
SHH, WNT pathway, PCP pathway, convergent extension
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.
SHH, patched, smoothened, GLI
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.
SHH, morphogen
118
______ signaling is involved in many developmental events, including establishing the midline and left—right asymmetry and in patterning many different organs.
SHH
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.
PCP, WNT, FRIZZLED, CELSR, VANGL, DISHEVELLED
