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Hormonal and Molecular Regulation of Phallus Differentiation in a Marsupial Tammar Wallaby

by Yu Chen 1,2,* and Marilyn B. Renfree 2,*
1
Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, FL 32603, USA
2
School of BioSciences, The University of Melbourne, Parkville, VIC 3010, Australia
*
Authors to whom correspondence should be addressed.
Genes 2020, 11(1), 106; https://doi.org/10.3390/genes11010106 (registering DOI)
Received: 9 December 2019 / Revised: 24 December 2019 / Accepted: 14 January 2020 / Published: 16 January 2020
(This article belongs to the Special Issue Marsupial Genetics and Genomics)
Congenital anomalies in phalluses caused by endocrine disruptors have gained a great deal of attention due to its annual increasing rate in males. However, the endocrine-driven molecular regulatory mechanism of abnormal phallus development is complex and remains largely unknown. Here, we review the direct effect of androgen and oestrogen on molecular regulation in phalluses using the marsupial tammar wallaby, whose phallus differentiation occurs after birth. We summarize and discuss the molecular mechanisms underlying phallus differentiation mediated by sonic hedgehog (SHH) at day 50 pp and phallus elongation mediated by insulin-like growth factor 1 (IGF1) and insulin-like growth factor binding protein 3 (IGFBP3), as well as multiple phallus-regulating genes expressed after day 50 pp. We also identify hormone-responsive long non-coding RNAs (lncRNAs) that are co-expressed with their neighboring coding genes. We show that the activation of SHH and IGF1, mediated by balanced androgen receptor (AR) and estrogen receptor 1 (ESR1) signalling, initiates a complex regulatory network in males to constrain the timing of phallus differentiation and to activate the downstream genes that maintain urethral closure and phallus elongation at later stages. View Full-Text
Keywords: lncRNA; WGCNA; marsupial; androstanediol; RNAseq; IGF1; SHH; oestrogen; castration; phallus lncRNA; WGCNA; marsupial; androstanediol; RNAseq; IGF1; SHH; oestrogen; castration; phallus
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Chen, Y.; Renfree, M.B. Hormonal and Molecular Regulation of Phallus Differentiation in a Marsupial Tammar Wallaby. Genes 2020, 11, 106.

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