Dev108944 1..11

Murine lacrimal, harderian and meibomian glands develop from the prospective conjunctival and eyelid epithelia and produce secretions that lubricate and protect the ocular surface. Sox9 expression localizes to the presumptive conjunctival epithelium as early as E11.5 and is detected in the lacrimal and harderian glands as they form. Conditional deletion showed that Sox9 is required for the development of the lacrimal and harderian glands and contributes to the formation of the meibomian glands. Sox9 regulates the expression of Sox10 to promote the formation of secretory acinar lobes in the lacrimal gland. Sox9 and FGF signaling were required for the expression of cartilageassociated extracellular matrix components during early stage lacrimal gland development. Fgfr2 deletion in the ocular surface epithelium reducedSox9and eliminatedSox10 expression.Sox9deletion from the ectoderm did not affect Fgf10 expression in the adjacent mesenchyme or Fgfr2 expression in the epithelium, but appeared to reduce FGF signaling.Sox9heterozygotes showedahaploinsufficient phenotype, in which the exorbital branch of the lacrimal gland was absent in most cases.However, enhancementofepithelialFGFsignalingbyexpression of a constitutively active FGF receptor only partially rescued the lacrimal gland defects in Sox9 heterozygotes, suggesting a crucial role of Sox9, downstreamofFGFsignaling, in regulating lacrimal glandbranchingand