Essential roles for the Abl and Arg tyrosine kinases in neurulation.
The Abl and Arg tyrosine kinases play fundamental roles in the development and function of the central nervous system. Arg is most abundant in adult mouse brain, especially in synapse-rich regions. arg(-/-) mice develop normally but exhibit multiple behavioral abnormalities, suggesting that arg(-/-) brains suffer from defects in neuronal function. Embryos deficient in both Abl and Arg suffer from defects in neurulation and die before 11 days postcoitum (dpc). Although they divide normally, abl(-/-)arg(-/-) neuroepithelial cells display gross alterations in their actin cytoskeleton. We find that Abl and Arg colocalize with each other and with actin microfilaments at the apical surface of the developing neuroepithelium. Thus, Abl and Arg play essential roles in neurulation and can regulate the structure of the actin cytoskeleton.
Koleske
A J
AJ
Department of Biology, Massachusetts Institute of Technology, Cambridge 02139, USA. anthony.koleske@yale.edu
Gifford
A M
AM
Scott
M L
ML
Nee
M
M
Bronson
R T
RT
Miczek
K A
KA
Baltimore
D
D
D000199:Actins / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000002:abnormalities / Q000196:embryology / Q000502:physiology*; D003433:Crosses, Genetic; D003599:Cytoskeleton / Q000473:pathology; D005260:Female; D005313:Fetal Death; D008297:Male; D001523:Mental Disorders / Q000196:embryology / Q000235:genetics / Q000503:physiopathology; D051379:Mice; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009421:Nervous System Malformations / Q000196:embryology*; D009474:Neurons / Q000473:pathology / Q000502:physiology*; D011505:Protein-Tyrosine Kinases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D016315:Proto-Oncogene Proteins c-abl / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction; D013569:Synapses / Q000502:physiology*; D013950:Thymus Gland / Q000502:physiology
D000199:Actins; D008869:Microtubule-Associated Proteins; D011993:Recombinant Fusion Proteins; D011505:Protein-Tyrosine Kinases; D016315:Proto-Oncogene Proteins c-abl