Neural tube defects by NUAK1 and NUAK2 double mutation.
BACKGROUND
NUAK1 and NUAK2, members of the AMP-activated protein kinase family of serine/threonine kinases, are prominently expressed in neuroectoderm, but their functions in neurulation have not been elucidated.


RESULTS
NUAK1 and NUAK2 double mutants exhibited exencephaly, facial clefting, and spina bifida. Median hinge point was formed, but dorsolateral hinge point formation was not apparent in cranial neural plate; neither apical constriction nor apico-basal elongation took place efficiently in the double mutants during the 5-10-somite stages. Concomitantly, the apical concentration of phosphorylated myosin light chain 2, F-actin, and cortactin was insignificant, and development of acetylated α-tubulin-positive microtubules was poor. However, the distribution of F-actin, cortactin, Shroom3, Rho, myosin heavy chain IIB, phosphorylated myosin light chain 2, α-tubulin, γ-tubulin, or acetylated α-tubulin was apparently normal in the double mutant neuroepithelia at the 5-somite stage.


CONCLUSIONS
NUAK1 and NUAK2 complementarily function in the apical constriction and apico-basal elongation that associate with the dorsolateral hinge point formation in cephalic neural plate during the 5- to 10-somite stages. In the double mutant neural plate, phosphorylated myosin light chain 2, F-actin, and cortactin did not concentrate efficiently in apical surfaces, and acetylated α-tubulin-positive microtubules did not develop significantly.
Laboratory for Vertebrate Body Plan, Center for Developmental Biology, RIKEN Kobe, Kobe, Japan.
Tomomi
T
Ohmura
Go
G
Shioi
Mariko
M
Hirano
Shinichi
S
Aizawa
D000818:Animals; D015153:Blotting, Western; D017403:In Situ Hybridization; D051379:Mice; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D009154:Mutation; D054259:Neural Tube / Q000002:abnormalities* / Q000378:metabolism*; D054261:Neurulation / Q000235:genetics / Q000502:physiology; D011494:Protein Kinases / Q000235:genetics* / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D012097:Repressor Proteins; D011494:Protein Kinases; C571903:NUAK1 protein, mouse; D017346:Protein Serine-Threonine Kinases