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