Calcium signals drive cell shape changes during zebrafish midbrain-hindbrain boundary formation.
One of the first morphogenetic events in the vertebrate brain is the formation of the highly conserved midbrain-hindbrain boundary (MHB). Specific cell shape changes occur at the point of deepest constriction of the MHB, the midbrain-hindbrain boundary constriction (MHBC), and are critical for proper MHB formation. These cell shape changes are controlled by nonmuscle myosin II (NMII) motor proteins, which are tightly regulated via the phosphorylation of their associated myosin regulatory light chains (MRLCs). However, the upstream signaling pathways that initiate the regulation of NMII to mediate cell shape changes during MHB morphogenesis are not known. We show that intracellular calcium signals are critical for the regulation of cell shortening during initial MHB formation. We demonstrate that the MHB region is poised to respond to calcium transients that occur in the MHB at the onset of MHB morphogenesis and that calcium mediates phosphorylation of MRLC specifically in MHB tissue. Our results indicate thatcalmodulin 1a(calm1a), expressed specifically in the MHB, and myosin light chain kinase together mediate MHBC cell length. Our data suggest that modulation of NMII activity by calcium is critical for proper regulation of cell length to determine embryonic brain shape during development.
Department of Biological Sciences, University of Wisconsin-Milwaukee, Milwaukee, WI 53201.
Srishti U
SU
Sahu
Department of Biological Sciences, University of Wisconsin-Milwaukee, Milwaukee, WI 53201.
Mike R
MR
Visetsouk
Department of Biological Sciences, University of Wisconsin-Milwaukee, Milwaukee, WI 53201.
Ryan J
RJ
Garde
Department of Biological Sciences, University of Wisconsin-Milwaukee, Milwaukee, WI 53201.
Leah
L
Hennes
Department of Biological Sciences, University of Wisconsin-Milwaukee, Milwaukee, WI 53201.
Constance
C
Kwas
Department of Biological Sciences, University of Wisconsin-Milwaukee, Milwaukee, WI 53201 gutzman@uwm.edu.
Jennifer H
JH
Gutzman
D000818:Animals; D001921:Brain / Q000196:embryology / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D048430:Cell Shape / Q000235:genetics / Q000502:physiology*; D047108:Embryonic Development; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D008636:Mesencephalon / Q000196:embryology / Q000378:metabolism; D020409:Molecular Motor Proteins / Q000378:metabolism; D009024:Morphogenesis; D024462:Myosin Type II / Q000378:metabolism*; D038081:Organogenesis; D010766:Phosphorylation; D012249:Rhombencephalon / Q000196:embryology / Q000378:metabolism; D015398:Signal Transduction; D015027:Zebrafish / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism
D020409:Molecular Motor Proteins; D029961:Zebrafish Proteins; D024462:Myosin Type II; D002118:Calcium