The primary behaviors of the mature lower urinary tract (LUT) - storage and voiding depend on a functional nervous system. Development of these circuits in the prenatal period is poorly understood. Postnatal, there is a dramatic transition frm the immature situation where voiding is """"""""automatic"""""""", i.e., not controlled by brain-driven processes, to the healthy mature system where filling triggers a conscious need to void, but micturition is determined voluntarily at an appropriate time and place. Around puberty, further changes occur to coordinate bladder, bowel and sexual activity. Many events occur in the nervous system over these periods, although the cellular loci and molecular mechanisms have not been defined. The goals of this molecular anatomy GUDMAP Atlas Project are to map (i) the detailed temporal and spatial profiles of axon connections that form with the mouse lower urinary tract during pre- and postnatal periods, and (ii) the expression of factors/receptors that may initiate and sustain these connections. The project will use robust neuroanatomical methods including tract tracing, immunohistochemistry and in situ hybridization to address three aims: (1) To map the terminal fields of key functional and chemical classes of sensory and motor axons within the mouse LUT during development and postnatal maturation;(2) To define the structural and chemical """"""""fingerprint"""""""" of sensory and autonomic neurons innervating the mouse LUT during this period;(3) To map the cellular source of neurotrophic and guidance factors that determine connectivity between nerves and the mouse LUT. Constructing this knowledge base is essential to understand how these connections form (or fail to form) and the mechanisms that may sustain or modulate them in health, disease or injury states. Establishing a structural and chemical fingerprint of developing and mature bladder neurons will also allow researchers to interpret many of the current expression patterns in the GUDMAP database. More broadly, the outcomes will promote understanding of these developing and maturing circuits and provide a strong foundation to analyze plasticity and injury responses in the developing and adult urogenital system.

Public Health Relevance

This project will map the development and maturation of nerve connections with the lower urinary tract, and the proteins that control the growth of these nerves. This is important because genetic defects in these nerves or injury to them in adults, requires solutions to replace them or to stimulate growth of new connections. The project will provide promote the development of new strategies to address these needs.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project--Cooperative Agreements (U01)
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Special Emphasis Panel (ZDK1-GRB-R (O2))
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Hoshizaki, Deborah K
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University of Melbourne
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Keast, Janet R; Smith-Anttila, Casey J A; Osborne, Peregrine B (2015) Developing a functional urinary bladder: a neuronal context. Front Cell Dev Biol 3:53
Georgas, Kylie M; Armstrong, Jane; Keast, Janet R et al. (2015) An illustrated anatomical ontology of the developing mouse lower urogenital tract. Development 142:1893-908