Neurturin regulates postnatal differentiation of parasympathetic pelvic ganglion neurons, initial axonal projections, and maintenance of terminal fields in male urogenital organs

Abstract

We have investigated the development of autonomic nerves in the urogenital tract of male mice and the effect of neurturin gene deletion on this process. At birth, autonomic innervation of the reproductive organs was sparse, but urinary bladder smooth muscle was well innervated. Further innervation of reproductive tissues occurred until P21, but noradrenergic axons established their complete terminal field later than nitrergic cholinergic axons: in adults the former are more prevalent, yet this became apparent only at P7 (vas deferens, seminal vesicles), P14 (prostate) or after P14 (penis). Neurturin was essential for initial projection of axons (mucosa of vas deferens), maintenance of terminal fields (prostate and seminal vesicles), or both functions (cavernosum of penis). In contrast, some targets (e.g., bladder muscle and suburothelium, vas deferens smooth muscle) were unaffected by neurturin gene deletion. Pelvic ganglion neurons more than doubled between birth and adulthood, probably as aresult of continued maturation of p75-positive undifferentiated neuronal precursors rather than cell division. The adult number of neurons was achieved by P7 (sympathetic) or P21 (parasympathetic). In adult neurturin knockout mice, there were approximately 25% fewer parasympathetic neurons compared with wild types, because of failure of differentiation after P14. This study revealed the complexity of postnatal maturation of urogenital innervation, with each organ showing a distinct chronology of innervation and different requirement for neurturin. Our results also indicate that in adults there will be distinct differences in neurturin dependence between organs, such that proregenerative therapies may have to be tailored specifically for the nerve pathway of interest.

An illustrated anatomical ontology of the developing mouse lower urogenital tract

“…9G,H) (Wiese et al, 2012) and whole adult bladders (Fig. 9J-L) (Yan and Keast, 2008), tissues were immunostained as described previously. For IF of tissues from Swiss Webster (Fig.…”

“…For IF (Fig. 9I,N-P,Q-S), cryosections (14-20 µm thickness) were processed according to described methods (Yan and Keast, 2008;Wiese et al, 2012).…”

Neurochemical phenotype of cytoglobin-expressing neurons in the rat hippocampus

“…The primary antibodies employed for IHC were: i) Rabbit anti-Cygb [in-house, code# 5092/6, 1:3,000 dilution and characterized previously (9,12,13)]; ii) sheep anti-nNOS [Dr Emson, University of Cambridge (Cambridge, UK), 1:3,000 dilution and characterized previously (24,25)]. nNOS produces the gas-neurotransmitter NO, which is involved in a number of physiological and pathological processes, including vasodilatation and RNS-mediated damage.…”

Decrease in neuronal nicotinic acetylcholine receptor subunit and PSD-93 transcript levels in the male mouse MPG after cavernous nerve injury or explant culture

“…The development and differentiation of many parasympathetic postganglionic neurons and enteric ganglia are supported by members of the glial-derived neurotrophic factor family, such as neurturin (22,23). Consequently, we postulated that one signal contributing to the decrease in nAChR subunit and PSD-93 transcript expression might be a loss of target-derived neurturin.…”