An immunohistochemical study of TLR-4 and -7 expression during murine embryonic development: respiratory apparatus and peripheral nervous system

Abstract

Toll-Like receptors (TLRs) are the mammalian orthologue of the type-I transmembrane

receptor Toll originally identifi ed in Drosophila for its function in embryonic developmental

patterning [1]. In mammals, TLRs are known to function in innate immunity by recognizing

molecular motifs unique to pathogens or injured tissue. However, literature data are emerging

about a morphogenetic role of TLRs during development also in mammals, in particular

of the nervous system [2]. We assessed TLRs expression in murine peripheral nervous system

during the embryonic development, focusing on the innervation of the respiratory apparatus.

Mouse embryos from stages E12 to E18 were excised, fi xed in paraformaldehyde and paraffi n

embedded. Immunohistochemical stainings were performed to study the expression of TLR4

and TLR7, and to visualize the developing peripheral nervous system by the neural marker

beta-3 tubulin. TLR7 immunoreactivity was already present at E12 in the dorsal root ganglia

(DRG) and in the nodose ganglion and, by E14, in the sympathetic ganglia (PVG), vagus nerve,

and also in nervous fi bers and ganglia in the respiratory apparatus. Instead, TLR4 started to be

weakly detected at E14 in DRG, PVG, and vagus nerve and, by E17, also in the smooth muscle,

nervous fi bers, and little ganglia of the respiratory apparatus. In conclusion the earlier expression

of TLR7 could suggest for this receptor a role in the developmental processes while, the

late detection of TLR4 might indicate it is most probably related to the maturation of immunity

mechanisms in preparation for birth.