Inactivation of Dicer1 in Steroidogenic factor 1-positive cells reveals tissue-specific requirement for Dicer1in adrenal, testis, and ovary

Abstract

BackgroundThe synthesis of microRNA (miRNA) is a multi-step process that requires the action of the ribonuclease Dicer1. Dicer1 is responsible for the final processing of miRNA and has been implicated in cellular processes such as proliferation, apoptosis, and differentiation. Mouse embryos lacking Dicer1 die in early embryogenesis. In this study, we investigated whether Dicer1 is required for development of adrenal, testis, and ovary in mouse embryos.ResultsTo target Dicer1 deletion specifically in developing adrenals and gonads, we used Steroidogenic factor 1-cre (Sf1/Cre) line in which Cre recombinase is active in the progenitor cells of adrenals and gonads. Lack of Dicer1 in the SF1-positive cells did not affect formation and early differentiation of the adrenals and gonads. However, increasing numbers of apoptotic cells were first detected in the Dicer1 knockout adrenal cortex at 18.5 days post coitum (dpc), followed by apoptosis of somatic cells and germ cells in the testis at postnatal day 0. Affected adrenal and testes underwent complete degeneration 48 hrs after the onset of apoptosis. However, ovaries were not affected at least until postnatal day 5, when the animals died due to adrenal insufficiency.ConclusionsDicer1 is dispensable for formation and differentiation of fetal tissues derived from the SF1-positive adrenogonadal primordium. Dicer1 is essential for maintaining cell survival in adrenal and testis; however, development of the ovary from fetal stages to postnatal day 5 does not require the presence of Dicer1. Our results reveal a tissue-specific requirement of Dicer1 and microRNAs. Future research is needed to understand how the tissue-specific role of Dicer1 is established.

Good planning and serendipity: exploiting the Cre/Lox system in the testis

“…No reporter expression was detected in GCs. The early onset of the Cre (reporter expression detectable at E10.5) has lead to exploitation of this line for studies of gonadogenesis (Kim et al 2007, Maatouk et al 2008, Barsoum et al 2009, Krentz et al 2009, Huang & Yao 2010.…”

MicroRNA-24 Is a Novel Regulator of Aldosterone and Cortisol Production in the Human Adrenal Cortex

“…However, few studies have investigated their impact on the regulation of corticosteroid production, and their role in adrenal gland pathophysiology remains poorly understood. Targeted deletion of Dicer elicits effects on adrenal cell development and survival, 14 and miRNAs are also known to be dysregulated in adrenal carcinomas.15 Although the regulation of aldosterone production by miR-21 has been demonstrated, no direct effect on specific target mRNAs was shown. 16 Here, we investigate the post-transcriptional effects of miRNAs on CYP11B2 and CYP11B1 expression and on corticosteroid production in the human adrenal cortex.…”

The role of non-coding RNAs in male sex determination and differentiation

“…Surprisingly, depending on the experimental setup, there is little overlap between the different studies with respect to the miRNAs that were detected (e.g., Papaioannou et al 2009, Aguilar et al 2010, Rakoczy et al 2013. In addition, deletion of Dicer or Drosha demonstrated only a relatively late role for miRNAs in the postnatal testis (Hayashi et al 2008, Maatouk et al 2008, Papaioannou et al 2009, Huang & Yao 2010, suggesting that miRNAs might not play a role during the early stages of sex differentiation. However, miRNAs appear to be very stable, at least in the testis, resulting in a loss of all miRNAs only after several days following Dicer deletion (Papaioannou et al 2009).…”

“…Mice homozygous for Dicer1 deletion in either germ or somatic cells during embryogenesis lead to male infertility due to multiple cumulative defects resulting in the absence of functional sperm (Hayashi et al 2008, Maatouk et al 2008, Papaioannou et al 2009, Huang & Yao 2010, Zimmermann et al 2014, demonstrating that miRNAs are important for proper testis development and function. However, from these experiments it remains unclear which specific miRNAs play important roles in these processes.…”