Developmental Genetics Flashcards
How many segments correspond to pair-rule genes in Drosophila?
7
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
Apical Ectodermal Ridge (AER)
What are the features of 46, XY DSD atypical gonad formation?
Abnormal gonads:
- Streak gonads of fibrous tissue (dysgenesis)
- Female ducts and variable female external genitalia
What are the characteristics of Hox genes expressed towards the 5’ end of the DNA?
They are expressed more posterior later in development
Definition
a protein that creates a posterior-to-anterior slope and is a morphogen that helps in abdomen formation
Nanos
What are the features of 46, XX DSD atypical gonad formation?
Abnormal gonads:
- Testicular or partially testicular gonads
- Male external genitalia
- Infertility
True or False:
Specification is irreversible fate commitment
False
Specification is flexible; cells can still be influenced by extrinsic factors
Define
Transcription factor
a DNA-binding protein that bonds to specific sequences adjacent to or within the promotor region of a gene; regulates gene transcription
What is the gene hierarchy of a Drosophila body plan?
- Maternal effect genes
- Gap genes
- Pair-rule genes
- Segment polarity genes
- Homeotic selector
What signalling molecule is secreted by dorsal ectoderm?
Wnt7a
Definition
a family of cell signalling proteins that are involved in a wide variety of processes, most notably as crucial elements for normal development
Fibroblast growth factor (Fgf)
What do gap and pair-rule genes encode?
Transcription factors
What interacts with the AER to regulate proximal-distal patterning?
Mesoderm
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
Homeotic transformations
Define
Segment polarity genes
genes that regulate the spatial pattern of differentiation within each segment of the developing Drosophila embryo
Definition
genes expressed as stripes around the blastoderm embryo during development of the Drosophila embryo
Pair-rule genes
Definition
a DNA-binding protein that bonds to specific sequences adjacent to or within the promotor region of a gene; regulates gene transcription
Transcription factor
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
Somite
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
Fgf8
Which genes are required for ovary development?
R-SPO1
WNT4
True or False
Sox gene products interact with DNA similar to Hox gene products
True
Except they bind to the minor groove instead of the major groove
Define
Homeodomain
part of the protein that attaches (binds) to specific regulatory regions of the target genes
Define
Organogenesis
the production and development of the organs of an animal or plant
What do homeotic selector genes do?
Specify the characteristic structures of each segment (i.e. thorax with legs)
Definition
medical conditions involving the development of the reproductive system
Disorders of Sex Development
What commonly happens to the SRY gene 46, XY feminised patients?
It gets deleted
What is the name given to a gene that influences more than one developmental process/phenotypic trait?
Pleiotropic gene
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
Definition
a group of signal transduction pathways which begin with proteins that pass signals into a cell through cell surface receptors
Wnt
Define
Autopod
The distal major subdivision of a limb (hand or foot)
How do limb buds form?
Mesenchymal cells migrate out to form a bulge
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
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
Definition
the production and development of the organs of an animal or plant
Organogenesis
What do the Wolffian ducts become in males?
Nothing, they regress
Definition
A section of an animal’s limb corresponding to the forearm.
Zeugopod
Definition
genes that regulate the spatial pattern of differentiation within each segment of the developing Drosophila embryo
Segment polarity genes
Define
Stylopod
the upper part of the arm in limb development
In Drosophila, which important molecules are encoded by segment polarity genes?
Wingless and Hedgehog
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.
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
What are the two main maternal mRNAs that set up anterior-posterior axis in Drosophila?
Bicoid and nanos
Cells that spend the most time in the progress have a more _______ fate
distal
Define
Hunchback
a gene required for segmentation of an anterior and posterior region of the Drosophila embryo
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
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
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
Definition
a gene required for segmentation of an anterior and posterior region of the Drosophila embryo
Hunchback
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
Low concentrations of Shh leads to a more __________ development
Anterior (i.e. thumb)
What does R-SPO1 mutations cause in humans?
XX male development
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
Complete this image
Nano protein ________ translation of caudal mRNA and ________ hunchback
Does not effect; represses
What do mutants of homeotic genes cause?
Homeotic transformations
What is the most common cause of 46, XY DSD?
Partial or complete androgen insensitivity syndrome
How does SRY affect R-spo1?
SRY inhibits the inhibitory effects of R-spo1 allowing male development
Define
Morphogenesis
the biological process that causes an organism to develop its shape
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
How many Hox clusters do Drosophila have?
1
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
Which human digit develops due to high concentrations of Shh?
Pinky
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
What is the human ortholog of wingless?
Wnt
How many categories are there in the Prader scale?
Seven
Which models are used to study limb morphogenesis?
Mouse and chicken
What type of genes set up anterior-posterior polarity in Drosophila?
Maternal effect genes
What commonly happens to the SRY gene in 46, XX masculinised patients?
Aberrant translocation onto the X chromosome
What controls the anterior-posterior axis of the limb?
Zone of polarising activity (ZPA)
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
Label this image of the limb bud
The organisation of tissues (ecto-, meso- or endoderm-derived) into organs is collectively known as what?
Organogenesis
What type of cell does Wnt4 and R-spo1 expression occur in females?
Granulosa cell
What do transgenic XX mice carrying the SRY gene develop into?
Male mice with testes
Label this image
What is massively parallel sequencing (MPS)?
A technique where the whole genome is sequenced and compared to parental samples
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
How do BMPs control the ventral development of a limb?
BMPs activate Engrailed in the ventral ectoderm which represses Wnt7a leading to ventral development
Definition
the upper part of the arm in limb development
Stylopod
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
Label this image
Label the following image of segment polarity gene action
Supporting cells in the male embryo become what?
Sertoli cells of seminiferous cords
Complete this image
Definition
The distal major subdivision of a limb (hand or foot)
Autopod
Define
Pleiotropy
condition in which a single mutation causes multiple phenotypic effects
What causes cells to commit to a fate?
Cell-cell signalling
A subset of _________ gene series is involved in anterior-posterior patterning
Hoxd
Is hunchback a maternal effect or a gap gene?
Gap gene
Label this image
Definition
the developmental process by which cells acquire different identities, depending on their relative spatial positions within the embryo
Pattern formation
Germ cells in a male embryo become what?
Spermatozoa
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
Define
Paralog
Two or more genes in the same species derived from duplication and subsequent divergence from a single ancestral gene
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
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
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
Which maternal mRNA sets up the anterior end of Drosophila embryo?
Bicoid
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
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
Label this image
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
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
Definition
part of the protein that attaches (binds) to specific regulatory regions of the target genes
Homeodomain
Definition
Two or more genes in the same species derived from duplication and subsequent divergence from a single ancestral gene
Paralog
True or False:
R-SPO1, as well as Wnt4, binds to the Frizzled receptor, activating β-catenin
True
46, XX DSD can be explained by ______-of-function of R-spo1/Wnt4 or ______-of-function of SRY/Sox9
Loss; gain
Which human digit develops due to low Shh concetrations?
Thumb
Definition
a maternal effect genes that are important in the formation of more posterior abdominal segments of the Drosophila embryo
Caudal (gene)
Define
Engrailed
a homeodomain transcription factor involved in many aspects of multicellular development
True or False
90% of 46, XX DSD is caused by SRY translocation onto X
True or False
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)
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
Which signalling molecule precisely defines where limb buds will form?
Fgf10
Define
Sonic Hedgehog (SHH)
key inductive signal in patterning of the anterior-posterior limb axis, the ventral somites and the ventral neural tube
Which genes and signalling molecules are involved in testis development?
SRY
SOX9
FGF9
Which germ layer controls dorso-ventral patterning in the developing limb?
Ectoderm
Definition
condition in which a single mutation causes multiple phenotypic effects
Pleiotropy
Define
Disorders of Sex Development
medical conditions involving the development of the reproductive system
What is the master sex-determining gene in mammals?
SRY
Which dot is exposure to the highest concentrations of Fgfs?
Yellow (then red, then white)
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
What is the Apical Ectodermal Ridge required for?
Limb outgrowth and proximal-distal development
Definition
a maternal effect gene whose protein concentration gradient patterns the anterior-posterior (A-P) axis during Drosophila embryogenesis
Bicoid
What are the characteristics of Hox genes expressed towards the 3’ end of the DNA?
They are expressed more anterior earlier in development
Which cells in male mice express SRY?
Sertoli cells
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
Define
Zeugopod
A section of an animal’s limb corresponding to the forearm.
What does this interaction lead to?
Limb bud outgrowth
Define
Syncytium
a single cell or cytoplasmic mass containing several nuclei, formed by fusion of cells or by division of nuclei
What does an overexpression of Shh cause?
Digit defects (i.e. extra digits)
Which chromosome of Drosophila are homeotic selector genes found on?
III
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
What do the Mullerian ducts become in females?
Uterus and fallopian tubes
Define
Pair-rule genes
genes expressed as stripes around the blastoderm embryo during development of the Drosophila embryo
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
True or False:
Cytokinesis between nuclei is occurring during the action of segment polarity genes
True
Definition
key inductive signal in patterning of the anterior-posterior limb axis, the ventral somites and the ventral neural tube
Sonic Hedgehog (SHH)
What is the phenotype of XX humans with loss-of-function mutations in R-spo1?
Males with testes
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
What are the two ducts that are initially present in both sexes?
Wolffian and Mullarian ducts
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)
Define
Caudal (gene)
a maternal effect genes that are important in the formation of more posterior abdominal segments of the Drosophila embryo
Define
Pattern formation
the developmental process by which cells acquire different identities, depending on their relative spatial positions within the embryo
46, XY DSD can explained by ________-of-function of R-spo1/Wnt4 or ________-of-function of SRY/SRY-regulators/SOX9
Gain; loss
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)
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
Definition
a single cell or cytoplasmic mass containing several nuclei, formed by fusion of cells or by division of nuclei
Syncytium
What phenotypic feature does Drosophila Segment-polarity gene mutants have?
Mutants show defects in every segment
How does the AER sustain outgrowth of the limb bud?
The release of Fgfs that keep cells proliferating underneath the AER
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
What signalling molecule is induced by R-SPO1?
Wnt4
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
True or False:
R-SPO1 is expressed in both male and female embryonic gonads
False
It is expressed in female but not male gonads
Definition
a secreted protein that interacts with WNT4 in the process of female sex development in humans
R-spondin1 (R-SPO1)
What phenotypic feature does Drosophila pair-rule gene mutants have?
Mutants lack portions of every other segment
What is the name of the receptor that Wnt binds to?
Frizzled
Steroidogenic cells in a male embryo become what?
Leydig cells
What would this lead to?
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
True or False:
The Zone of Polarising Activity (ZPA) is an anterior signalling centre
False
It is a posterior signalling centre
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
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
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
How many Hox clusters do humans have?
4
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
True or False:
90% of 46, XY DSD is caused by SRY mutation
False
66% have unknown cause
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)
What are each of the stripes expressed by pair-rules defined by?
Different types of upstream regulators/enhancers control different stripes
What is the phenotype of Lim1 null mice?
Paws with two ventral surfaces
Which part of the DNA do homeodomains bind to?
Major groove
Define
Wnt
a group of signal transduction pathways which begin with proteins that pass signals into a cell through cell surface receptors
What is the most common cause of 46, XX DSD?
Congenital adrenal hyperplasia
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
Definition
a homeodomain transcription factor involved in many aspects of multicellular development
Engrailed
What phenotypic feature does Drosophila gap gene mutants have?
Missing (“gaps”) in body segments
A loss-of-function mutation in 21-hydroxylase causes what?
Congenital adrenal hyperplasia - build up of testosterone
Which model of limb development does this image display?
Progress zone model
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
Define
R-spondin1 (R-SPO1)
a secreted protein that interacts with WNT4 in the process of female sex development in humans
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
Bicoid protein ________ translation of caudal mRNA and _________ hunchback
Represses; activates
What are the two broad categories of Disorders of Sex Development?
- Gonads can be “normal” but external genitalia atypical
- Both gonad and external genitalia can be atypical
Is caudal a maternal effect or a gap gene?
Maternal effect
Which morphogen is responsible for anterior-posterior limb development?
Sonic hedgehog (Shh)
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
Which model of limb development does this image depict?
Which maternal mRNA sets up the posterior end of the Drosophila embryo?
Nanos
Define
Nanos
a protein that creates a posterior-to-anterior slope and is a morphogen that helps in abdomen formation
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
How many units does segment polarity genes divide the embryo into?
14 units
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
What is the sex genotype and phenotype of individuals with AIS?
Chromosomally male (XY) but outwardly female body
Define
Bicoid
a maternal effect gene whose protein concentration gradient patterns the anterior-posterior (A-P) axis during Drosophila embryogenesis
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)
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
True or False:
Prior to further segmentation by pair-rule genes, the embryo is still a syncytium
True
Definition
the biological process that causes an organism to develop its shape
Morphogenesis
True or False:
Determination is irreversible fate commitment
True
