19 Developmental Genetics Flashcards
What is needed for an organism to grow form a single cell?
Differential gene expression
What are the 4 developmental patterns that can be gained from animal models?
Axis specification. Pattern formation. Organogenesis. Induction/polarity
What are the six animal models mentioned and their scientific names?
C.elegans(nematode) D.melanogaster(fruit fly) D.rerio(zebrafish) X.laevis(clawed frog) G.gallus(chicken) M.musculus(mouse)
Pro/con of C.elegans model
Short generation, know cell fate/invertebrate
Pro/con of D.melanogaster model
Short gen, easy breeding, high mutation/maintenance
Pro/con of D.rerio model
Transparent embryo, easy breeding/small embryo
Pro/con of X.laevis model
Large embryo/tetraploid
Pro/con of G.gallus model
Large embryo/genetics difficult (genome is mapped now however)
Pro/con of M.musculus model
Easy breeding, mammal/embryo small
Which genetic mediators interact between nearby cells?
Paracrine signaling molecules
Which genetic mediators control gene expression and respond to external stimuli?
DNA transcription factors
Which genetic mediators facilitate migration and is scaffolding?
Extracellular Matrix proteins
What are the four mentioned paracrine signaling molecules?
Fibroblast Growth factor(FGF), Hedgehog proteins, Wingless family(Wt), Transforming growth factor beta(TGF-beta)
What can be affected in paracrine signaling mutations?
Receptor or molecule
What expresses FGFR3?
Growing bones
What results from FGFR mutations?
Autosomal dominant, skeletal dysplasias depending on how severe
What are the three forms of FGFR3 mutation phenotypes?
Achondroplasia - most common, short limbs, microcephaly // hypochondroplasia - milder form // thanatophoric dysplasia - lethal, very short limbs, receptor highly activated
What are the three mentioned transcription factors mentioned?
Homeobox - HOX //High mobility group - SOX // T-box - TBX
What is the archetype of the SOX family
SRY gene of Y -> regulates SOX9, high in males, low in females, mammalian testis determining factor
What does SOX9 regulate? What will mutation do?
Chondrogenesis and Col2A1. Mutation = camptomelic dysplasia = short limbs, female XY
What is Hirschsprung diseases and what gene of the SOX family can cause it?
Neural crest defect causing colon hypomobility, males 4x risk, SOX10 mutation
What are the four main ECM proteins mentioned?
Collagens, fibrilins, elastin and laminin
What disease results from Type I collagen gene mutation?
Osteogenesis imperfecta due to mutation in glycine within fibrils = bone disruptions mild to lethal
What can a mutation of Fibrillin 1 and elastin cause?
Marfan’s syndrome leading to heart and large blood vessel problems along
What are the phenotypic results of marfans?
Tall/lanky, arachnodactyly, lens displacement
What can a mutation of laminin gene LAMC2 cause?
Junctional epidemoylysis bullosa leading to large blisters on the skin
What is the function of laminin?
Anchors cells to ECM
What is pattern formation?
How tissues and organs are established thus position and cell differentiation
What processes is Sonic Hedgehog SHH gene involved in?
Neural tube/somite/limbs and the left-right axis
What is cell fate?
Type, fxn and longevity
What results form a severe defect in SHH gene cause?
Midline brain development leading to holoprosencephaly
What does the SHH bind to?
Membrane Cholesterol
Which genes are the axes of the body determined by?
4 clusters of put to 13 genes = 39 total HOX genes
genes in the same relative position (ie. HOX) are called?
Paralogs
Define temporal colinearity and spatial colinearity
Temporal - genes on the 3’ end will be expressed sooner//Spatial - genes on the 3’ will be expressed more at the “front”(anterior) of the protein sequence
Define Homeotic transformation
When HOX genes are not in correct sequence/combination -> affected area transforms to another part
What signals define the Ventral axis? Dorsal? Lateral?
Ventral - Bmp4 // Dorsal - Noggin, Chordin binds off Bmp4 // Lateral - equal amounts of SHH
Laterality defects can cause what two anomalies?
Situs ambiguus or situs inversus
With a ZIC3 protein what may occur in males and females?
Males - situs ambiguus // females - situs inversus
Which is a candidate gene for limb induction and what maintains its expression?
FGF8 of the mesoderm induces, WNT2b/8c maintains its expression
Growth of the limb bud is stimulated by which three signals?
FGF2/4/8
The zone of polarizing activity(ZPA) uses what to maintain the apical ectodermal ridge?
SHH
What is a typical anterior axis defect, signs and gene affected?
Holt-Oram syndrome leading to shortened or missing radius and thumbs. T-box gene TBX5 is mutated
What is a typical posterior axis defect, signs and gene affected?
Ulnar mammary leading to deformed upper limbs and chest on the ulnar side. TBX3 gene (related to TBX5) is responsible
What gene drives pancreatic development, maturation, differentiation as well as insulin release?
IPF1
What are two animal models used commonly to test specific genes as well as its effect upon deletion?
Transgenic and knockout mice
