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15 Cards in this Set
- Front
- Back
- 3rd side (hint)
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The same gene...
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--Is operational at different periods of development or
--Operates in different regions/organs -- Reduces the overall number of molecules needed for the embryo |
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Fundamental Molecular Mechanisms of Differentiation/Development
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(1) Gene regulation by transcription factors
(2) Cell-cell interactions by direct contact (inductions) or morphogens (signaling molecules) (3) Cell movement/migration (4) Alteration of cell shape and polarity (5) Programmed cell death (apoptosis) |
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Transcription Factors
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Produced by developmental genes
Control RNA transcription from DNA Bind to specific regulatory DNA sequences Tend to work within the cell that they're produce Examples of TF's? |
Basic helix-loop-helix proteins --Regulate myogenesis
Zinc finger proteins --Regulate Y chromosome genes --Insert into DNA helix Homeobox proteins --contains 60 aa DNA BD --coded by 180nt homeobox (HOX) gene |
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HOX Genes
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Genes are arranged along the chromosome in a very specific order
Expressed in a specific order 3’ region expressed earlier>>>cranial structures 5’ region expressed later>>>caudal structures 11 Position of the gene on the chromosome is co-linear with both timing of expression and location of expression within the embryo What axis do they determine? Involved in formation of? |
HOX genes determine patterning along the cranio- caudal axis
HOX genes involved in formation of: - CNS - Axial skeleton and limbs - GI tract - GU tract |
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TF's with homeobox domains/other conserved sequences
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PAX
SOX Lim T-Box Dlx What does each help develop? |
PAX: sense organs, CNS
SOX: cartilage, sex differentiation T-Box: Limb differentiation Dlx: patterning/outgrowing structures |
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Signaling Molecules (Morphogens or Cytokines) Major Families
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TGF β (transforming GF beta) family
FGF (fibroblast GF) family Wnt (wingless) family Hedgehog family |
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TGF β (transforming GF beta) family locations of expression, effects
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Mesodermal induction/patterning
Active in somites BMP (bone morphogenic protein) Initiation of gastrulation Active in notocord Induction of neural plate |
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FGF Signaling Molecules
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FGF1: early liver induction
FGF2: limb buds/hair growth/renal tubules FGF3: inner ear FGF 10: limb and lung induction |
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Wnt Signaling Molecules
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Functions as a dorsal-specific gene
ONLY EXPRESSED DORSALLY Role in limb development |
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Hedgehog family of signaling molecules - role and function
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Organizer of early embryo
Shh - Determines Dorsal/ventral (A/P) Axis Secreted in high level by notocord Important in determining asymmetry of hand How does Shh function? |
inhibits Patched's inhibiton of Smoothened
Smoothened--> released Zn finger TF form MT in cell; downstream gene expression |
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Receptor Molecules Function and Example
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Notch receptor and lateral inhibition
--inhibition of neural development, creating a glial cell instead --Notch receptor activated by Delta; intracellular domain--> cascade, directs neuronal development |
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Molecular development process of the limb
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Embryonic week 4-5:
HOX genes turn on FGF10 FGF10 activates FGF8 FGF8 + TBX5=upper ext. FGF8 + TBX4=lower ext. |
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Molecular basis of Outgrowth of Limb
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FGF8+FGF4>> Apical Ectodermal Ridge
AER>>outgrowth of limb HOXA and HOXD clusters expressed 29 proximal (3') > distal (5') |
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Molecular Regions of Limb Development
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AER
Progress zone ZPA Dorsal ectoderm Ventral ectoderm What happens in each? |
AER --> FGF 2,4,8
Progress zone --> HOX A, D, WNT, BMP ZPA --> Shh expression Dorsal ectoderm --> Wnt-7A Ventral ectoderm -->En-1 (engrailed) |
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Molecular basis of formation of digits
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TBX1 causes apoptosis, leads to fingers and toes
2,3-polydactyly common |
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