entwickslungmechanik developmental mechanisms. morphogenesis 5 major questions of morphology how is...
TRANSCRIPT
Entwickslungmechanik
Developmental Mechanisms
Morphogenesis
5 Major Questions of MorphologyHow is polarity achievedHow are locations determined How are tissues formed from cellsHow are organs formed from tissuesHow is the growth of organs coordinated
Morphogenesis
Migration of cellsOften layers of cells moving as sheetsRequires extracellular matrices & ECM
adhesion moleculesECM proteins - laminin, fibronectinAdhesion molecules – integrins, CAMs
MorphogenesisMigrating Fibroblasts showing lamellipodia
MorphogenesisCranial Neural Crest Migration into the Branchial Arches
Migrating cells require ECM such as laminin or fibronectin on which to travel
Migrating cells express various combinations of integrin proteins
Integrins are connected within the cell to intermediate filaments and the actin cytoskeleton
Sites of adhesion are called Focal Adhesion Points (FAPs)
Morphogenesis
Morphogenesis
Morphogenesis
Sorting of cellsBoundaries between regions within the
embryo must be formed Forming organs Regions of the CNS
Requires that cells do not mixPreventing cell adhesion prevents
migration and mixing of cell populations
MorphogenesisRhombomeres in the hindbrain and their associated neural crest form distinct segments
Morphogenesis
Differential cell adhesion
1st demonstrated by Holtfreter (1955)Differential affinities among early
embryonic cell types
Morphogenesis Holtfreter & Townes 1955
Morphogenesis
Morphogenesis Differential adhesion
hypothesis (1964 Steinberg) Explains cell sorting by
thermodynamic principles Aggregates form with the
lowest interfacial free energy (most thermodynamically stable arrangement)
Either different cell adhesion molecules are present or different concentrations of them are present
Morphogenesis Cadherin proteins mediateCell-cell adhesion via homotypic interaction of cadherin extracellular domains
Classical CadherinsEP/C-cadherin – embryonicE-cadherin – epithelialN-cadherin – neural P-cadherin – placental
Non-classicalmany genes
Morphogenesis
Depletion of maternal -catenin results in dissociation of blastomeres in Xenopus
Expression of dominant-negative E-cadherin in Xenopus results in improper cell migrations and lack of neural tube closure
Morphogenesis