PAR-1 kinase functions in establishment of epithelial cell polarity and in notch-mediated lateral inhibition during Drosophila neurogenesis

PAR-1 function in Drosophila is required at the earliest stage of development, during oogenesis. This serine-threonine kinase first acts in oocyte specification, and then in polarization events within the oocyte that establish the anterior-posterior axis of the future embryo. PAR-1 is expressed throughout Drosophila development, but its function has not been extensively characterized beyond oogenesis due to oocyte lethality of null mutants. We removed maternal and zygotic par-1 by RNAi to circumvent the genetic limitation for analysis of null embryos. Pre-cellularized embryos injected with par-1 dsRNA were assayed at different developmental stages. A requirement for PAR-1 in establishing cell polarity within the blastoderm epithelium was revealed. PAR-1 restricts adherens junction proteins to the apico-lateral membrane of epithelia. Absence of PAR-1 expanded localization of DE-cadherin, phospho-Tyrosine and Patj antibodies along lateral epithelial surfaces and increased their presence in cytoplasm. Other abnormalities observed in epithelia were abnormal Crumbs localization within the apical membrane and increased Tau in the apical cytoplasm, which suggests increased microtubule density. Further analyses within larval eye imaginal discs indicate PAR-1 is not essential for maintenance of epithelial cell polarity, but is required for normal morphogenesis. Additionally, we present a novel role for PAR-1 in Notch-mediated lateral inhibition during embryonic neurogenesis. Our epistasis data indicate PAR-1 functions upstream of Notch.