Entwickslungmechanik Developmental Mechanisms

Morphogenesis 5 Major Questions of Morphology  How is polarity achieved  How are locations determined  How are tissues formed from cells  How are organs formed from tissues  How is the growth of organs coordinated

Morphogenesis Migration of cells  Often layers of cells moving as sheets  Requires extracellular matrices & ECM adhesion molecules  ECM proteins - laminin, fibronectin  Adhesion molecules – integrins, CAMs

Morphogenesis Migrating Fibroblasts showing lamellipodia

Morphogenesis Cranial 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

Sorting of cells  Boundaries between regions within the embryo must be formed  Forming organs  Regions of the CNS  Requires that cells do not mix  Preventing cell adhesion prevents migration and mixing of cell populations

Morphogenesis Rhombomeres in the hindbrain and their associated neural crest form distinct segments

Morphogenesis Differential cell adhesion  1 st demonstrated by Holtfreter (1955)  Differential affinities among early embryonic cell types

Morphogenesis Holtfreter & Townes 1955

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 mediate Cell-cell adhesion via homotypic interaction of cadherin extracellular domains Classical Cadherins EP/C-cadherin – embryonic E-cadherin – epithelial N-cadherin – neural P-cadherin – placental Non-classical many 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