Integrins have been implicated in various processes of nervous system 
development, including proliferation, migration, and differentiation of neuronal 
cells. In this study, we show that the serine/threonine kinase Ndr2 controls 
integrin-dependent dendritic and axonal growth in mouse hippocampal neurons. We 
further demonstrate that Ndr2 is able to induce phosphorylation at the activity- 
and trafficking-relevant site Thr(788/789) of β1-integrin to stimulate the PKC- 
and CaMKII-dependent activation of β1-integrins, as well as their exocytosis. 
Accordingly, Ndr2 associates with integrin-positive early and recycling 
endosomes in primary hippocampal neurons and the surface expression of activated 
β1-integrins is reduced on dendrites of Ndr2-deficient neurons. The role of Ndr2 
in dendritic differentiation is also evident in vivo, because Ndr2-null mutant 
mice show arbor-specific alterations of dendritic complexity in the hippocampus. 
This indicates a role of Ndr2 in the fine regulation of dendritic growth; in 
fact, treatment of primary neurons with Semaphorin 3A rescues Ndr2 
knock-down-induced dendritic growth deficits but fails to enhance growth beyond 
control level. Correspondingly, Ndr2-null mutant mice show a Semaphorin 
3A(-/-)-like phenotype of premature dendritic branching in the hippocampus. The 
results of this study show that Ndr2-mediated integrin trafficking and 
activation are crucial for neurite growth and guidance signals during neuronal 
development.