Adhesion G-protein-coupled receptor, GPR56, is required for Müllerian duct development in the chick

The embryonic Müllerian ducts give rise to the female reproductive tract (fallopian tubes, uterus and upper vagina in humans, the oviducts in birds). Embryonic Müllerian ducts initially develop in both sexes, but later regress in males under the influence of anti-Müllerian hormone. While the molecular and endocrine control of duct regression in males have been well studied, early development of the ducts in both sexes is less well understood. Here, we describe a novel role for the adhesion G protein-coupled receptor, GPR56, in development of the Müllerian ducts in the chicken embryo. GPR56 is expressed in the ducts of both sexes from early stages. The mRNA is present during the elongation phase of duct formation, and it is restricted to the inner Müllerian duct epithelium. The putative ligand, Collagen III, is abundantly expressed in the Müllerian duct at the same developmental stages. Knockdown of GPR56 expression using in ovo electroporation results in variably truncated ducts, with a loss of expression of both epithelial and mesenchymal markers of duct development. Over-expression of GPR56 in vitro results in enhanced cell proliferation and cell migration. These results show that GPR56 plays an essential role in avian Müllerian duct development through the regulation of duct elongation.

Download Full-text

Transcriptional landscape of the embryonic chicken Müllerian duct

BMC Genomics ◽

10.1186/s12864-020-07106-8 ◽

2020 ◽

Vol 21 (1) ◽

Author(s):

Zahida Yesmin Roly ◽

Rasoul Godini ◽

Martin A. Estermann ◽

Andrew T. Major ◽

Roger Pocock ◽

...

Keyword(s):

Cell Migration ◽

Neuronal Cell ◽

Female Reproductive Tract ◽

Unknown Etiology ◽

Mullerian Duct ◽

Female Reproduction ◽

Müllerian Duct ◽

Mullerian Ducts ◽

Duct Development ◽

Transcriptional Landscape

Abstract Background Müllerian ducts are paired embryonic tubes that give rise to the female reproductive tract in vertebrates. Many disorders of female reproduction can be attributed to anomalies of Müllerian duct development. However, the molecular genetics of Müllerian duct formation is poorly understood and most disorders of duct development have unknown etiology. In this study, we describe for the first time the transcriptional landscape of the embryonic Müllerian duct, using the chicken embryo as a model system. RNA sequencing was conducted at 1 day intervals during duct formation to identify developmentally-regulated genes, validated by in situ hybridization. Results This analysis detected hundreds of genes specifically up-regulated during duct morphogenesis. Gene ontology and pathway analysis revealed enrichment for developmental pathways associated with cell adhesion, cell migration and proliferation, ERK and WNT signaling, and, interestingly, axonal guidance. The latter included factors linked to neuronal cell migration or axonal outgrowth, such as Ephrin B2, netrin receptor, SLIT1 and class A semaphorins. A number of transcriptional modules were identified that centred around key hub genes specifying matrix-associated signaling factors; SPOCK1, HTRA3 and ADGRD1. Several novel regulators of the WNT and TFG-β signaling pathway were identified in Müllerian ducts, including APCDD1 and DKK1, BMP3 and TGFBI. A number of novel transcription factors were also identified, including OSR1, FOXE1, PRICKLE1, TSHZ3 and SMARCA2. In addition, over 100 long non-coding RNAs (lncRNAs) were expressed during duct formation. Conclusions This study provides a rich resource of new candidate genes for Müllerian duct development and its disorders. It also sheds light on the molecular pathways engaged during tubulogenesis, a fundamental process in embryonic development.

Download Full-text

Mechanistic Drivers of Müllerian Duct Development and Differentiation Into the Oviduct

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.605301 ◽

2021 ◽

Vol 9 ◽

Author(s):

Laura Santana Gonzalez ◽

Ioanna A. Rota ◽

Mara Artibani ◽

Matteo Morotti ◽

Zhiyuan Hu ◽

...

Keyword(s):

Epithelial Cells ◽

Embryonic Development ◽

Progenitor Cells ◽

Female Reproductive Tract ◽

Mullerian Duct ◽

Genetic Determinants ◽

Mesenchymal Transition ◽

Müllerian Duct ◽

Mullerian Ducts ◽

Duct Development

The conduits of life; the animal oviducts and human fallopian tubes are of paramount importance for reproduction in amniotes. They connect the ovary with the uterus and are essential for fertility. They provide the appropriate environment for gamete maintenance, fertilization and preimplantation embryonic development. However, serious pathologies, such as ectopic pregnancy, malignancy and severe infections, occur in the oviducts. They can have drastic effects on fertility, and some are life-threatening. Despite the crucial importance of the oviducts in life, relatively little is known about the molecular drivers underpinning the embryonic development of their precursor structures, the Müllerian ducts, and their successive differentiation and maturation. The Müllerian ducts are simple rudimentary tubes comprised of an epithelial lumen surrounded by a mesenchymal layer. They differentiate into most of the adult female reproductive tract (FRT). The earliest sign of Müllerian duct formation is the thickening of the anterior mesonephric coelomic epithelium to form a placode of two distinct progenitor cells. It is proposed that one subset of progenitor cells undergoes partial epithelial-mesenchymal transition (pEMT), differentiating into immature Müllerian luminal cells, and another subset undergoes complete EMT to become Müllerian mesenchymal cells. These cells invaginate and proliferate forming the Müllerian ducts. Subsequently, pEMT would be reversed to generate differentiated epithelial cells lining the fully formed Müllerian lumen. The anterior Müllerian epithelial cells further specialize into the oviduct epithelial subtypes. This review highlights the key established molecular and genetic determinants of the processes involved in Müllerian duct development and the differentiation of its upper segment into oviducts. Furthermore, an extensive genome-wide survey of mouse knockout lines displaying Müllerian or oviduct phenotypes was undertaken. In addition to widely established genetic determinants of Müllerian duct development, our search has identified surprising associations between loss-of-function of several genes and high-penetrance abnormalities in the Müllerian duct and/or oviducts. Remarkably, these associations have not been investigated in any detail. Finally, we discuss future directions for research on Müllerian duct development and oviducts.

Download Full-text

Faculty Opinions recommendation of G protein-coupled receptor 56 and collagen III, a receptor-ligand pair, regulates cortical development and lamination.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.13411036.14782161 ◽

2011 ◽

Author(s):

Masayasu Kojima

Keyword(s):

G Protein ◽

Cortical Development ◽

G Protein Coupled Receptor ◽

Receptor Ligand ◽

Collagen Iii ◽

G Protein Coupled

Download Full-text

Mechanism for Adhesion G Protein-Coupled Receptor GPR56-Mediated RhoA Activation Induced By Collagen III Stimulation

PLoS ONE ◽

10.1371/journal.pone.0100043 ◽

2014 ◽

Vol 9 (6) ◽

pp. e100043 ◽

Cited By ~ 35

Author(s):

Rong Luo ◽

Sung-Jin Jeong ◽

Annie Yang ◽

Miaoyun Wen ◽

David E. Saslowsky ◽

...

Keyword(s):

G Protein ◽

G Protein Coupled Receptor ◽

Rhoa Activation ◽

Collagen Iii ◽

G Protein Coupled

Download Full-text

G protein-coupled receptor 56 and collagen III, a receptor-ligand pair, regulates cortical development and lamination

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1104821108 ◽

2011 ◽

Vol 108 (31) ◽

pp. 12925-12930 ◽

Cited By ~ 158

Author(s):

R. Luo ◽

S.-J. Jeong ◽

Z. Jin ◽

N. Strokes ◽

S. Li ◽

...

Keyword(s):

G Protein ◽

Cortical Development ◽

G Protein Coupled Receptor ◽

Receptor Ligand ◽

Collagen Iii ◽

G Protein Coupled

Download Full-text

Embryological basis of malformed female genital tract and various classifications

National Journal of Clinical Anatomy ◽

10.1055/s-0039-3401756 ◽

2014 ◽

Vol 03 (03) ◽

pp. 150-158

Author(s):

Richa Niranjan ◽

A K Singh ◽

Anjoo Yadav

Keyword(s):

Management Strategies ◽

Female Genital Tract ◽

Mullerian Duct ◽

Bicornuate Uterus ◽

Müllerian Duct ◽

Uterine Malformation ◽

Müllerian Duct Anomalies ◽

Mullerian Ducts ◽

Mullerian Duct Anomalies ◽

Duct Development

AbstractDevelopmental anomalies of the Mullerian duct system represent some of the most fascinating disorders that obstetricians and gynaecologists encounter. The uterus is formed during embryogenesis by the fusion of the two paramesonephric ducts (Mullerian ducts). This process usually fuses the two Mullerian ducts into a single uterine body, but fails to take place in the affected women who maintain their double Mullerian systems. A bicornuate uterus is a type of a uterine malformation where upper part of uterus forms two horns. The fusion process of upper part of Mullerian duct is altered. As a result, cranial part of the uterus becomes bifurcated. As Mullerian duct anomalies are of anatomic interest, this article discusses epidemiology, embryological development, genetics of development and malformation and lastly various classifications based on Mullerian duct development. Pregnancy in bicornuate uterus is usually of high risk with reproductive outcomes like recurrent abortions, preterm delivery or malpresentation. Classifying Mullerian duct anomalies bears merit because it correlates anatomic anomalies with arrests in morphogenesis. Establishing an accurate diagnosis is essential for planning treatment and management strategies.

Download Full-text