Developmental Genetics Flashcards
1
Q
How many segments correspond to pair-rule genes in Drosophila?
A
7
2
Q
Definition
a structure that forms from the ectodermal cells at the distal end of each limb bud and acts as a major signaling center to ensure proper development of a limb
A
Apical Ectodermal Ridge (AER)
3
Q
What are the features of 46, XY DSD atypical gonad formation?
A
Abnormal gonads:
- Streak gonads of fibrous tissue (dysgenesis)
- Female ducts and variable female external genitalia
4
Q
What are the characteristics of Hox genes expressed towards the 5’ end of the DNA?
A
They are expressed more posterior later in development
5
Q
Definition
a protein that creates a posterior-to-anterior slope and is a morphogen that helps in abdomen formation
A
Nanos
6
Q
What are the features of 46, XX DSD atypical gonad formation?
A
Abnormal gonads:
- Testicular or partially testicular gonads
- Male external genitalia
- Infertility
7
Q
True or False:
Specification is irreversible fate commitment
A
False
Specification is flexible; cells can still be influenced by extrinsic factors
8
Q
Define
Transcription factor
A
a DNA-binding protein that bonds to specific sequences adjacent to or within the promotor region of a gene; regulates gene transcription
9
Q
What is the gene hierarchy of a Drosophila body plan?
A
- Maternal effect genes
- Gap genes
- Pair-rule genes
- Segment polarity genes
- Homeotic selector
10
Q
What signalling molecule is secreted by dorsal ectoderm?
A
Wnt7a
11
Q
Definition
a family of cell signalling proteins that are involved in a wide variety of processes, most notably as crucial elements for normal development
A
Fibroblast growth factor (Fgf)
12
Q
What do gap and pair-rule genes encode?
A
Transcription factors
13
Q
What interacts with the AER to regulate proximal-distal patterning?
A
Mesoderm
14
Q
Definition
a mutation that causes a tissue normally determined to form a specific organ or body part to alter its pathway of differentiation and form another structure
A
Homeotic transformations
15
Q
Define
Segment polarity genes
A
genes that regulate the spatial pattern of differentiation within each segment of the developing Drosophila embryo
16
Q
Definition
genes expressed as stripes around the blastoderm embryo during development of the Drosophila embryo
A
Pair-rule genes
17
Q
Definition
a DNA-binding protein that bonds to specific sequences adjacent to or within the promotor region of a gene; regulates gene transcription
A
Transcription factor
18
Q
Definition
each of a number of body segments containing the same internal structures, clearly visible in invertebrates such as earthworms but also present in the embryonic stages of vertebrates
A
Somite
19
Q
Definition
A growth factor important and necessary for setting up and maintaining the midbrain/hindbrain border which plays the vital role of “organizer” in development
A
Fgf8
20
Q
Which genes are required for ovary development?
A
R-SPO1
WNT4
21
Q
True or False
Sox gene products interact with DNA similar to Hox gene products
A
True
Except they bind to the minor groove instead of the major groove
22
Q
Define
Homeodomain
A
part of the protein that attaches (binds) to specific regulatory regions of the target genes
23
Q
A
24
Q
Define
Organogenesis
A
the production and development of the organs of an animal or plant
25
What do homeotic selector genes do?
Specify the characteristic structures of each segment (i.e. thorax with legs)
26
# Definition
medical conditions involving the development of the reproductive system
Disorders of Sex Development
27
What commonly happens to the SRY gene 46, XY feminised patients?
It gets deleted
28
What is the name given to a gene that influences more than one developmental process/phenotypic trait?
Pleiotropic gene
29
# Define
Determination
establishment of a specific pattern of gene activity and developmental fate for a given cell, usually prior to any manifestation of the cell's future phenotype
30
# Definition
a group of signal transduction pathways which begin with proteins that pass signals into a cell through cell surface receptors
Wnt
31
# Define
Autopod
The distal major subdivision of a limb (hand or foot)
32
How do limb buds form?
Mesenchymal cells migrate out to form a bulge
33
# Define
Somite
each of a number of body segments containing the same internal structures, clearly visible in invertebrates such as earthworms but also present in the embryonic stages of vertebrates
34
# Define
Fgf8
A growth factor important and necessary for setting up and maintaining the midbrain/hindbrain border which plays the vital role of “organizer” in development
35
# Definition
the production and development of the organs of an animal or plant
Organogenesis
36
37
What do the Wolffian ducts become in males?
Nothing, they regress
38
# Definition
A section of an animal's limb corresponding to the forearm.
Zeugopod
39
# Definition
genes that regulate the spatial pattern of differentiation within each segment of the developing Drosophila embryo
Segment polarity genes
40
# Define
Stylopod
the upper part of the arm in limb development
41
In Drosophila, which important molecules are encoded by segment polarity genes?
Wingless and Hedgehog
42
# Define
Bone Morphogenetic Protein (BMP)
a group of growth factors also known as cytokines considered to constitute a group of pivotal morphogenetic signals, orchestrating tissue architecture throughout the body.
43
44
# Define
Segmentation genes
a gene involved in the early stages of pattern formation that define repeated units (metameres) in a segmented organism, usually the embryo
45
What are the two main maternal mRNAs that set up anterior-posterior axis in Drosophila?
Bicoid and nanos
46
Cells that spend the most time in the progress have a more _______ fate
distal
47
# Define
Hunchback
a gene required for segmentation of an anterior and posterior region of the Drosophila embryo
48
Where would you expect to find seminiferous cords?
a. The undifferentiated gonad
b. The developing testis
c. The developing ovary
d. Sertoli cells
b. The developing testis
49
# Define
Colinearity
the linear relationship between the nucleotide sequence in a gene (or the RNA transcribed from it) and the order of amino acids in the polypeptide chain specified by the gene
50
# Define
Homeobox
a sequence of 180 nucleotides that encodes a sequence of 60 amino acids called a homeodomain, which is part of a DNA-binding protein that acts as a transcription factor
51
# Definition
a gene required for segmentation of an anterior and posterior region of the Drosophila embryo
Hunchback
52
True or False:
Hox genes are expressed in discrete domains along the A-P axis
False
They are expressed in overlapping domains, with each area having a unique combination of Hox gene expression
53
Low concentrations of Shh leads to a more __________ development
Anterior (i.e. thumb)
54
What does R-SPO1 mutations cause in humans?
XX male development
55
# Define
Gap genes
genes expressed in contiguous domains along the anterior-posterior axis of the Drosophila embryo that regulate the process of segmentation in each domain
56
Complete this image
57
Nano protein ________ translation of caudal mRNA and ________ hunchback
Does not effect; represses
58
What do mutants of homeotic genes cause?
Homeotic transformations
59
What is the most common cause of 46, XY DSD?
Partial or complete androgen insensitivity syndrome
60
How does SRY affect R-spo1?
SRY inhibits the inhibitory effects of R-spo1 allowing male development
61
# Define
Morphogenesis
the biological process that causes an organism to develop its shape
62
What are the features of 46, XX DSD abnormal testosterone action?
* Increased androgen action (e.g. increased testosterone in Congenital Adrenal Hyperplasia)
* Gonads normal ovaries but external genitalia and masculinised
63
How many Hox clusters do Drosophila have?
1
64
What is the fate of the Müllerian ducts in an XY embryo?
a. They are stimulated by testosterone
b. They become vas deferens and epididimys
c. They regress and disappear
d. They form the Fallopian tubes and uterus
c. They regress and disappear
65
Which human digit develops due to high concentrations of Shh?
Pinky
66
# Define
Homeotic selector (Hox) genes
genes that confer segment identity in Drosophila. They encode homeodomain proteins which interact with Hox and other homeotic genes to initiate segment-specific gene regulation. Homeodomain proteins are transcription factors that share a DNA-binding domain called the homeodomain
67
What is the human ortholog of wingless?
Wnt
68
How many categories are there in the Prader scale?
Seven
69
Which models are used to study limb morphogenesis?
Mouse and chicken
70
What type of genes set up anterior-posterior polarity in Drosophila?
Maternal effect genes
71
What commonly happens to the SRY gene in 46, XX masculinised patients?
Aberrant translocation onto the X chromosome
72
What controls the anterior-posterior axis of the limb?
Zone of polarising activity (ZPA)
73
# Definition
a secreted growth factor that acts in a paracrine fashion to reinforce the cell-autonomous activities of the transcription factors SRY and SOX9
Fgf9
74
Label this image of the limb bud
75
The organisation of tissues (ecto-, meso- or endoderm-derived) into organs is collectively known as what?
Organogenesis
76
What type of cell does Wnt4 and R-spo1 expression occur in females?
Granulosa cell
77
What do transgenic XX mice carrying the SRY gene develop into?
Male mice with testes
78
Label this image
79
What is massively parallel sequencing (MPS)?
A technique where the whole genome is sequenced and compared to parental samples
80
# Define
Sox9
a transcription factor that plays a pivotal role in male sexual development by producing a hormone in the Sertoli cells to inhibit the creation of a female reproductive system
81
How do BMPs control the ventral development of a limb?
BMPs activate Engrailed in the ventral ectoderm which represses Wnt7a leading to ventral development
82
# Definition
the upper part of the arm in limb development
Stylopod
83
# Definition
genes expressed in contiguous domains along the anterior-posterior axis of the Drosophila embryo that regulate the process of segmentation in each domain
Gap genes
84
Label this image
85
Label the following image of segment polarity gene action
86
Supporting cells in the male embryo become what?
Sertoli cells of seminiferous cords
87
Complete this image
88
# Definition
The distal major subdivision of a limb (hand or foot)
Autopod
89
# Define
Pleiotropy
condition in which a single mutation causes multiple phenotypic effects
90
What causes cells to commit to a fate?
Cell-cell signalling
91
A subset of _________ gene series is involved in anterior-posterior patterning
Hoxd
92
93
Is hunchback a maternal effect or a gap gene?
Gap gene
94
Label this image
95
# Definition
the developmental process by which cells acquire different identities, depending on their relative spatial positions within the embryo
Pattern formation
96
Germ cells in a male embryo become what?
Spermatozoa
97
What does the two signal model of limb development propose?
Proximal-distal patterning is controlled by the concentration gradients of retinoic acids and Fgfs. The higher the concentration of retinoic acid, the more proximal the cells. The higher the concentration of Fgfs, the more distal they become
98
# Define
Paralog
Two or more genes in the same species derived from duplication and subsequent divergence from a single ancestral gene
99
How does the R-spondin1 gene impact the β-catenin pathway leading to ovary development?
R-SPO1 stabilizes β-catenin, leading to target gene activation which results in ovary development
100
Why is bicoid called a “maternal effect gene?
a. It is made by the mother fly during egg production
b. It is deleted in female flies when the fly reproduces
c. It only has effects in female flies
d. The effects are only seen in the mother fly’s body
a. It is made by the mother fly during egg production
101
Ambiguous genitalia are detected at birth, how is this individual diagnosed?
* Sex chromosome karyotype: XX or XY
* Serum hormone measurements
* Examination of external genitalia and ultrasound of internal gonads
102
Which maternal mRNA sets up the anterior end of Drosophila embryo?
Bicoid
103
How are the 7 segments of the Drosophila turned into 14?
Segment polarity genes encode wingless and hedgehog. One row of cells express wingless and one row expresses hedgehog creating 14 segments
104
# Definition
a sequence of 180 nucleotides that encodes a sequence of 60 amino acids called a homeodomain, which is part of a DNA-binding protein that acts as a transcription factor
Homeobox
105
Label this image
106
Which homeobox transcription factor is involved in dorsal development of the limb? How is it activated?
Lim1 - activated by the expression of Wnt7a in dorsal ectoderm
107
# Define
Fgf9
a secreted growth factor that acts in a paracrine fashion to reinforce the cell-autonomous activities of the transcription factors SRY and SOX9
108
# Definition
part of the protein that attaches (binds) to specific regulatory regions of the target genes
Homeodomain
109
# Definition
Two or more genes in the same species derived from duplication and subsequent divergence from a single ancestral gene
Paralog
110
True or False:
R-SPO1, as well as Wnt4, binds to the Frizzled receptor, activating β-catenin
True
111
46, XX DSD can be explained by \_\_\_\_\_\_-of-function of R-spo1/Wnt4 or \_\_\_\_\_\_-of-function of SRY/Sox9
Loss; gain
112
Which human digit develops due to low Shh concetrations?
Thumb
113
# Definition
a maternal effect genes that are important in the formation of more posterior abdominal segments of the Drosophila embryo
Caudal (gene)
114
# Define
Engrailed
a homeodomain transcription factor involved in many aspects of multicellular development
115
True or False
90% of 46, XX DSD is caused by SRY translocation onto X
True or False
116
# Define
SRY
the sex-determining region of the Y chromosome, found near the chromosome's pseudoautosomal boundary. Accumulated evidence indicates that a gene in this region encodes the testis-determining factor (TDF)
117
# Definition
genes that confer segment identity in Drosophila. They encode homeodomain proteins which interact with Hox and other homeotic genes to initiate segment-specific gene regulation. Homeodomain proteins are transcription factors that share a DNA-binding domain called the homeodomain
Homeotic selector (Hox) genes
118
Which signalling molecule precisely defines where limb buds will form?
Fgf10
119
# Define
Sonic Hedgehog (SHH)
key inductive signal in patterning of the anterior-posterior limb axis, the ventral somites and the ventral neural tube
120
Which genes and signalling molecules are involved in testis development?
SRY
SOX9
FGF9
121
Which germ layer controls dorso-ventral patterning in the developing limb?
Ectoderm
122
# Definition
condition in which a single mutation causes multiple phenotypic effects
Pleiotropy
123
# Define
Disorders of Sex Development
medical conditions involving the development of the reproductive system
124
What is the master sex-determining gene in mammals?
SRY
125
Which dot is exposure to the highest concentrations of Fgfs?
Yellow (then red, then white)
126
# Definition
a situation where the phenotype of an organism is determined not only by the environment it experiences and its genotype, but also by the environment and genotype of its mother
Maternal effect
127
What is the Apical Ectodermal Ridge required for?
Limb outgrowth and proximal-distal development
128
# Definition
a maternal effect gene whose protein concentration gradient patterns the anterior-posterior (A-P) axis during Drosophila embryogenesis
Bicoid
129
What are the characteristics of Hox genes expressed towards the 3' end of the DNA?
They are expressed more anterior earlier in development
130
Which cells in male mice express SRY?
Sertoli cells
131
An example of a morphogen is:
a. A transcription factor that turns on a gene in a cell
b. A diffusible protein that influences cells via a concentration gradient
c. The morphology of an organ is due to several interacting cells
d. One factor turns on more that one other gene within the same cell
b. A diffusible protein that influences cells via a concentration gradient
132
# Define
Zeugopod
A section of an animal's limb corresponding to the forearm.
133
134
What does this interaction lead to?
Limb bud outgrowth
135
# Define
Syncytium
a single cell or cytoplasmic mass containing several nuclei, formed by fusion of cells or by division of nuclei
136
What does an overexpression of Shh cause?
Digit defects (i.e. extra digits)
137
Which chromosome of Drosophila are homeotic selector genes found on?
III
138
# Definition
the linear relationship between the nucleotide sequence in a gene (or the RNA transcribed from it) and the order of amino acids in the polypeptide chain specified by the gene
Colinearity
139
What do the Mullerian ducts become in females?
Uterus and fallopian tubes
140
# Define
Pair-rule genes
genes expressed as stripes around the blastoderm embryo during development of the Drosophila embryo
141
# Definition
the sex-determining region of the Y chromosome, found near the chromosome's pseudoautosomal boundary. Accumulated evidence indicates that a gene in this region encodes the testis-determining factor (TDF)
SRY
142
True or False:
Cytokinesis between nuclei is occurring during the action of segment polarity genes
True
143
# Definition
key inductive signal in patterning of the anterior-posterior limb axis, the ventral somites and the ventral neural tube
Sonic Hedgehog (SHH)
144
What is the phenotype of XX humans with loss-of-function mutations in R-spo1?
Males with testes
145
# Define
Fgf10
a paracrine signaling molecule seen first in the limb bud and organogenesis development. FGF10 starts the developing of limbs and its involved in the branching of morphogenesis in multiple organs such as the lungs, skin, ear and salivary glands
146
What are the two ducts that are initially present in both sexes?
Wolffian and Mullarian ducts
147
# Definition
a group of growth factors also known as cytokines considered to constitute a group of pivotal morphogenetic signals, orchestrating tissue architecture throughout the body.
Bone Morphogenetic Protein (BMP)
148
# Define
Caudal (gene)
a maternal effect genes that are important in the formation of more posterior abdominal segments of the Drosophila embryo
149
# Define
Pattern formation
the developmental process by which cells acquire different identities, depending on their relative spatial positions within the embryo
150
46, XY DSD can explained by \_\_\_\_\_\_\_\_-of-function of R-spo1/Wnt4 or \_\_\_\_\_\_\_\_-of-function of SRY/SRY-regulators/SOX9
Gain; loss
151
# Define
Congenital Adrenal Hyperplasia
a form of adrenal insufficiency in which the enzyme that produces two important adrenal steroid hormones, cortisol and aldosterone, is deficient. Because cortisol production is impeded, the adrenal gland instead overproduces androgens (male steroid hormones)
152
# Define
Zone of polarising activity (ZPA)
an area of mesenchyme that contains signals which instruct the developing limb bud to form along the anterior/posterior axis
153
# Definition
a single cell or cytoplasmic mass containing several nuclei, formed by fusion of cells or by division of nuclei
Syncytium
154
What phenotypic feature does Drosophila Segment-polarity gene mutants have?
Mutants show defects in every segment
155
How does the AER sustain outgrowth of the limb bud?
The release of Fgfs that keep cells proliferating underneath the AER
156
How does Wnt4 prevent β-catenin degradation?
Wnt molecule binds to the Frizzled receptor causing the recruitment of the LRP receptor which prevents the destruction complex from degrading β-catenin allowing it to enter the nucleus and influence gene expression
157
What signalling molecule is induced by R-SPO1?
Wnt4
158
# Define
Maternal effect
a situation where the phenotype of an organism is determined not only by the environment it experiences and its genotype, but also by the environment and genotype of its mother
159
True or False:
R-SPO1 is expressed in both male and female embryonic gonads
False
It is expressed in female but not male gonads
160
# Definition
a secreted protein that interacts with WNT4 in the process of female sex development in humans
R-spondin1 (R-SPO1)
161
What phenotypic feature does Drosophila pair-rule gene mutants have?
Mutants lack portions of every other segment
162
What is the name of the receptor that Wnt binds to?
Frizzled
163
Steroidogenic cells in a male embryo become what?
Leydig cells
164
What would this lead to?
165
# Define
Apical Ectodermal Ridge (AER)
a structure that forms from the ectodermal cells at the distal end of each limb bud and acts as a major signaling center to ensure proper development of a limb
166
True or False:
The Zone of Polarising Activity (ZPA) is an anterior signalling centre
False
It is a posterior signalling centre
167
# Definition
a transcription factor that plays a pivotal role in male sexual development by producing a hormone in the Sertoli cells to inhibit the creation of a female reproductive system
Sox9
168
169
What does the progress zone model of limb outgrowth propose?
Proximal-distal patterning is controlled by the amount of time a cell is exposed to Fgfs. The longer they are exposed, the more distal their fate
170
# Define
Fibroblast growth factor (Fgf)
a family of cell signalling proteins that are involved in a wide variety of processes, most notably as crucial elements for normal development
171
How many Hox clusters do humans have?
4
172
# Definition
establishment of a specific pattern of gene activity and developmental fate for a given cell, usually prior to any manifestation of the cell's future phenotype
Determination
173
True or False:
90% of 46, XY DSD is caused by SRY mutation
False
66% have unknown cause
174
What are the features of 46, XY DSD abnormal testosterone action?
* Gonads normal but defect in testosterone action leads to feminization (e.g. partial or complete Androgen Insensitivity Syndrome (AIS or PAIS)
175
What are each of the stripes expressed by pair-rules defined by?
Different types of upstream regulators/enhancers control different stripes
176
What is the phenotype of Lim1 null mice?
Paws with two ventral surfaces
177
Which part of the DNA do homeodomains bind to?
Major groove
178
# Define
Wnt
a group of signal transduction pathways which begin with proteins that pass signals into a cell through cell surface receptors
179
What is the most common cause of 46, XX DSD?
Congenital adrenal hyperplasia
180
# Definition
a form of adrenal insufficiency in which the enzyme that produces two important adrenal steroid hormones, cortisol and aldosterone, is deficient. Because cortisol production is impeded, the adrenal gland instead overproduces androgens (male steroid hormones)
Congenital Adrenal Hyperplasia
181
# Definition
a homeodomain transcription factor involved in many aspects of multicellular development
Engrailed
182
What phenotypic feature does Drosophila gap gene mutants have?
Missing ("gaps") in body segments
183
A loss-of-function mutation in 21-hydroxylase causes what?
Congenital adrenal hyperplasia - build up of testosterone
184
Which model of limb development does this image display?
Progress zone model
185
# Definition
a paracrine signaling molecule seen first in the limb bud and organogenesis development. FGF10 starts the developing of limbs and its involved in the branching of morphogenesis in multiple organs such as the lungs, skin, ear and salivary glands
Fgf10
186
# Define
R-spondin1 (R-SPO1)
a secreted protein that interacts with WNT4 in the process of female sex development in humans
187
True or False:
Loss of R-spo1 does not affect which sex pathway takes over
False
Loss of R-spo1 means male pathway is dominant
188
Bicoid protein ________ translation of caudal mRNA and _________ hunchback
Represses; activates
189
What are the two broad categories of Disorders of Sex Development?
1. Gonads can be "normal" but external genitalia atypical
2. Both gonad and external genitalia can be atypical
190
Is caudal a maternal effect or a gap gene?
Maternal effect
191
Which morphogen is responsible for anterior-posterior limb development?
Sonic hedgehog (Shh)
192
# Define
Homeotic transformations
a mutation that causes a tissue normally determined to form a specific organ or body part to alter its pathway of differentiation and form another structure
193
Which model of limb development does this image depict?
194
Which maternal mRNA sets up the posterior end of the Drosophila embryo?
Nanos
195
# Define
Nanos
a protein that creates a posterior-to-anterior slope and is a morphogen that helps in abdomen formation
196
As cells in the developing limb leave the progress zone what kind of fate do they have?
Proximal fate due to decreasing levels of Fgf exposure
197
How many units does segment polarity genes divide the embryo into?
14 units
198
True or False:
Homeotic genes are responsible for directly building characteristic structures
False
They provide positional information which tells the cell what it should do
199
What is the sex genotype and phenotype of individuals with AIS?
Chromosomally male (XY) but outwardly female body
200
# Define
Bicoid
a maternal effect gene whose protein concentration gradient patterns the anterior-posterior (A-P) axis during Drosophila embryogenesis
201
# Definition
an area of mesenchyme that contains signals which instruct the developing limb bud to form along the anterior/posterior axis
Zone of polarising activity (ZPA)
202
# Definition
a gene involved in the early stages of pattern formation that define repeated units (metameres) in a segmented organism, usually the embryo
Segmentation genes
203
True or False:
Prior to further segmentation by pair-rule genes, the embryo is still a syncytium
True
204
# Definition
the biological process that causes an organism to develop its shape
Morphogenesis
205
True or False:
Determination is irreversible fate commitment
True
