Lack of beta1 integrins in enteric neural crest cells leads to a Hirschsprung-like phenotype.

The enteric nervous system arises mainly from vagal and sacral neural crest cells that colonise the gut between 9.5 and 14 days of development in mice. Using the Cre-LoxP system, we removed beta1 integrins in the neural crest cells when they emerge from the neural tube.

Prototypical type I E-cadherin and type II cadherin-7 mediate very distinct adhesiveness through their extracellular domains.

Using a dual pipette assay that measures the force required to separate adherent cell doublets, we have quantitatively compared intercellular adhesiveness mediated by Type I (E- or N-cadherin) or Type II (cadherin-7 or -11) cadherins. At similar cadherin expression levels, cells expressing Type I cadherins adhered much more rapidly and strongly than cells expressing Type II cadherins. Using chimeric cadherins, we found that the extracellular domain exerts by far the dominant effect on cell adhesivity, that of E-cadherin conferring high adhesivity, and that of cadherin-7 conferring low adhesivity.

Force measurements in E-cadherin-mediated cell doublets reveal rapid adhesion strengthened by actin cytoskeleton remodeling through Rac and Cdc42.

We have used a modified, dual pipette assay to quantify the strength of cadherin-dependent cell-cell adhesion. The force required to separate E-cadherin-expressing paired cells in suspension was measured as an index of intercellular adhesion. Separation force depended on the homophilic interaction of functional cadherins at the cell surface, increasing with the duration of contact and with cadherin levels.

Conditional beta1-integrin gene deletion in neural crest cells causes severe developmental alterations of the peripheral nervous system.

Integrins are transmembrane receptors that are known to interact with the extracellular matrix and to be required for migration, proliferation, differentiation and apoptosis. We have generated mice with a neural crest cell-specific deletion of the beta1-integrin gene to analyse the role of beta1-integrins in neural crest cell migration and differentiation. This targeted mutation caused death within a month of birth.

The human tissue plasminogen activator-Cre mouse: a new tool for targeting specifically neural crest cells and their derivatives in vivo.

The ontogeny of neural crest cells (NCC) involves a number of orchestrated variety of derivatives, including components of the peripheral nervous system and melanocytes. Thus, it represents an excellent model system to investigate mechanisms controlling epithelial-mesenchymal transitions, cell migration and differentiation, as well as cell proliferation and death. We have established a new transgenic line expressing the Cre recombinase under the control of the human tissue plasminogen activator promoter (Ht-PA).