Integrin-mediated dendrite branch maintenance requires Abelson (Abl) family kinases.
Dendrite arbor structure is a critical determinant of nervous system function that must be actively maintained throughout life, but the signaling pathways that regulate dendrite maintenance are essentially unknown. We report that the Abelson (Abl) and Abl-related gene (Arg) nonreceptor tyrosine kinases are required for maintenance of cortical dendrites in the mouse brain. arg-/- cortical dendrites initially develop normally and are indistinguishable from wild-type dendrites at postnatal day 21. Dendrite branches are not efficiently maintained in arg-/- neurons, leading to a reduction in dendrite arbor size by early adulthood. More severe dendrite loss is observed in abl-/-arg-/- neurons. Elevation of Arg kinase activity in primary cortical neurons promotes axon and dendrite branching. Activation of integrin receptors by adhesion to laminin-1 or Semaphorin 7A also promotes neurite branching in cortical neurons, but this response is absent in arg-/- neurons because of the reduced dynamic behavior of mutant neurite branches. These data suggest that integrin signaling through Abl and Arg support cortical dendrite branch maintenance by promoting dendrite branch dynamics in response to adhesive cues.
Moresco
Eva Marie Yang
EM
Department of Genetics, Yale University School of Medicine, New Haven, Connecticut 06520-8024, USA.
Donaldson
Stephanie
S
Williamson
Anne
A
Koleske
Anthony J
AJ
D000199:Actins / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D002540:Cerebral Cortex / Q000201:enzymology / Q000502:physiology; D003001:Cloning, Molecular; D017931:DNA Primers; D003712:Dendrites / Q000201:enzymology / Q000502:physiology*; D016023:Integrins / Q000502:physiology*; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D011505:Protein-Tyrosine Kinases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D015183:Restriction Mapping
D000199:Actins; D017931:DNA Primers; D016023:Integrins; C426236:ARG tyrosine kinase; D011505:Protein-Tyrosine Kinases