Desert Hedgehog/Patched 1 signaling specifies fetal Leydig cell fate in testis organogenesis

Yao, Hisayuki; Whoriskey, Wendy; Capel, Blanche

doi:10.1101/gad.981202

Cited by 440 publications

(420 citation statements)

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“…Desert hedgehog (Dhh) and platelet-derived growth factor A (Pdfga), two Sertoli cell-derived signaling molecules, play an important role in differentiation of fetal Leydig cells (PierucciAlves et al, 2001;Yao et al, 2002;Brennan et al, 2003). Secreted by the Sertoli cell, Dhh acts in a paracrine fashion to induce the differentiation of both the fetal Leydig cells and of the peritubular myoid cells, surrounding the testicular cords (Yao et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

“…Secreted by the Sertoli cell, Dhh acts in a paracrine fashion to induce the differentiation of both the fetal Leydig cells and of the peritubular myoid cells, surrounding the testicular cords (Yao et al, 2002). Dhh activated signaling was suggested to trigger fetal Leydig cell differentiation by up-regulating SF-1 and cytochrome P450 side-chain cleavage (P450scc) expression in precursor cells located outside Page 4 of 34 A c c e p t e d M a n u s c r i p t 4 testis cords (Yao et al, 2002). Similarly, mutations in the gene encoding PDGF-A were found to attenuate the expression of P450scc and thereby disrupt early Leydig cell differentiation in mice (Gnessi et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

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Steroidogenesis and steroidogenic gene expression in postnatal fetal rat Leydig cells

Weisser¹,

Landreh²,

Söder³

et al. 2011

Molecular and Cellular Endocrinology

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Please cite this article as: Weisser, J., Landreh, L., Söder, O., Svechnikov, K., Steroidogenesis and steroidogenic gene expression in postnatal fetal rat Leydig cells, Molecular and Cellular Endocrinology (2008), doi:10.1016/j.mce.2011 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Our data indicate that cAMP-activated signaling pathway(s) play an important role in the regulation of PFLCs differentiation and function.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Steroidogenesis and steroidogenic gene expression in postnatal fetal rat Leydig cells

Weisser¹,

Landreh²,

Söder³

et al. 2011

Molecular and Cellular Endocrinology

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“…Peritubular myoid cells surround the testes cords and cooperate with pre-Sertoli cells to deposit the basal lamina and further define the testis cords. Signalling molecules produced by pre-Sertoli cells promote the differentiation of somatic cells found outside the cords into fetal Leydig cells, thus ultimately influencing the production of testosterone (Yao et al, 2002). Endothelial cells associate to form the coelomic vessel which promotes efficient export of testosterone.…”

Section: Introductionmentioning

confidence: 99%

Presumptive pre‐sertoli cells express genes involved in cell proliferation and cell signalling during a critical window in early testis differentiation

Cory

Boyer

Pilon

et al. 2007

Molecular Reproduction Devel

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In mammals, the pre-Sertoli cell of the male genital ridge is the first cell type to display sex specific differentiation and differential gene expression. The genetic cascade driving the differentiationof pre-Sertoli cells and ultimately testis formationis beginning to be unravelled, but many questions remain. A better understanding of the transcriptome of pre-Sertoli cells immediately after sex determination is essential in order to further understand this differentiationprocess. A mouse model expressing Red Fluorescent Protein (RFP) under the control of a hybrid mouse/pig SRY promoter (HybSRYp-RFP) was used to purify cells from embryonic day 12.0 (e12.0) male genital ridges. To compare the transcriptomes of HybSRYp-RFP cell populations versus age matched whole female genital ridges, RNA was extracted and used to generate molecular probes that were hybridized onto Affymetrix Mouse Genome 430 2.0 microarrays. The expression of genes considered markers for pre-Sertoli cells, including Sox9, Mis, Dhh and Fgf9 were identified within the HybSRYp-RFP expressing cell population, while markers for germ cells (Oct4, SSEA-1) and endothelial cells (Ntrk3) were not identified. In contrast, markers for ovarian somatic cell expression, including Fst and Bmp2, were identified as overexpressed within the ovarian cell population. In a general fashion, genes identified as 2.5-fold over expressed in HybSRYp-RFP expressing cells coded notably for cell signalling and extra cellular proteins. The expression of Sox10, Stc2, Fgf18, Fgf13 and Wnt6 were further characterized via whole mount in situ hybridization (WISH) on male and female genital ridges between e11.5 and e14.5. Sox10, Fgf18, Fgf13 and Stc2 gene expression was detected within the male genital ridges while Wnt6 was found diffusely within both the male and female genital ridges. These data represent the earliest comprehensive microarray expression analysis of purified presumptive pre-Sertoli cells available to date. Mol. Reprod. Dev. 74: 1491-1504, 2007

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“…For example, disruption of the GATA/FOG-2 interaction results in decreased expression of male-specific genes in the somatic cell lineages and in aberrant Leydig cell differentiation (Bielinska et al, 2007). Sertoli cell secreted factors such as desert hedgehog (Dhh) and genes expressed in Leydig cell precursors such as the Pdgf receptor-a and GATA-4 play key roles in modulating further differentiation of fetal Leydig cells (Yao et al, 2002;Brennan et al, 2003;Bielinska et al, 2007). Steroidogenicfactor 1 (SF-1), a gene expressed downstream of Sry, has a pivotal role in gonadal and adrenal organogenesis as well as being a transcriptional activator of steroid hydroxylases and other genes that are essential for androgen biosynthesis (Parker and Schimmer, 1997).…”

Section: Fetal Leydig Cellsmentioning

confidence: 99%

Key factors in the regulation of fetal and postnatal leydig cell development

Wan

Lee

2007

Journal Cellular Physiology

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The primary function of testicular Leydig cells is the production of androgens to promote sexual differentiation in the fetus, secondary sexual maturation at puberty, and spermatogenesis in the adult. The fetal and postnatal (adult) populations of Leydig cells differ morphologically and have distinct profiles of gene expression. As postnatal Leydig cells differentiate, they transition through three discrete maturational stages characterized by decreasing proliferative rate and increasing testosterone biosynthetic capacity. In this review, we discuss the development of both fetal and postnatal Leydig cells and review the regulation of this process by some of the key hormones and growth factors.

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Desert Hedgehog/Patched 1 signaling specifies fetal Leydig cell fate in testis organogenesis

Abstract: Establishment of the steroid-producing Leydig cell lineage is an event downstream of

Cited by 440 publications

References 49 publications

Steroidogenesis and steroidogenic gene expression in postnatal fetal rat Leydig cells

Steroidogenesis and steroidogenic gene expression in postnatal fetal rat Leydig cells

Presumptive pre‐sertoli cells express genes involved in cell proliferation and cell signalling during a critical window in early testis differentiation

Key factors in the regulation of fetal and postnatal leydig cell development

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