A ROLE FOR MESENCHYME-DERIVED TACHYKININS IN TOOTH AND MAMMARY-GLAND MORPHOGENESIS

Tachykinin peptides such as substance P (SP) function as neurotransmit ters and neuromodulators in the mammalian central and peripheral nervo us systems, Here, we provide evidence that they may also play an impor tant role in the morphogenesis of some nonneural organs where epitheli al-mesenchymal interactions are involved. We show the following, (1) m RNA encoding tachykinin precursor proteins is expressed transiently in condensing mesenchyme during the development of mouse tooth germ, mam mary gland, limb bud, external auditory meatus and genital tubercle, ( 2) In developing tooth germ and mammary gland; mRNA encoding the neutr al endopeptidase (NEP) that degrades secreted tachykinins is spatially and temporally co-expressed with tachykinin precursor mRNA, (3) SP an d the mRNA encoding SP receptors are also expressed in the developing tooth germ, (4) Tooth development in explant cultures is blocked both by tachykinin-precursor-specific antisense oligonucleotide and by an S P receptor antagonist: in both cases the block is relieved by exogenou s SP, Together, these findings suggest a surprising new role for tachy kinins in tooth and mammary gland morphogenesis, and possibly also in limb, ear and external genitalia morphogenesis.