Little is known about the key molecules that regulate cell division during organogenesis. Here we determine the role
of the cell cycle promoter aurora kinase B (AURKB) during development, using embryonic salivary glands (E-SGs) as a
model. AURKB is a serine/threonine kinase that regulates key events in mitosis, which makes it an attractive target for
tailored anticancer therapy. Many reports have elaborated on the role of AURKB in neoplasia and cancer; however, no
previous study has shown its role during organ development. Our previous experiments have highlighted the essential
requirement for AURKB during adult exocrine regeneration. To investigate if AURKB is similarly required for progression
during embryonic development, we pharmacologically inhibited AURKB in developing submandibular glands (SMGs)
at embryonic day (E)13.5 and E16.5, using the highly potent and selective drug Barasertib. Inhibition of AURKB
interfered with the expansion of the embryonic buds. Interestingly, this effect on SMG development was also seen
when the mature explants (E16.5) were incubated for 24 h with another cell cycle inhibitor Aphidicolin. Barasertib
prompted apoptosis, DNA damage and senescence, the markers of which (cleaved caspase 3, γH2AX, SA-βgal and p21,
respectively), were predominantly seen in the developing buds. In addition to a reduction in cell cycling and
proliferation of the epithelial cells in response to AURKB inhibition, Barasertib treatment led to an excessive generation
of reactive oxygen species (ROS) that resulted in downregulation of the acinar differentiation marker Mist1.
Importantly, inhibition of ROS was able to rescue this loss of identity, with Mist1 expression maintained despite loss of
AURKB. Together, these data identify AURKB as a key molecule in supporting embryonic development and
differentiation, while inhibiting senescence-inducing signals during organogenesis