DMRT proteins and coordination of mammalian spermatogenesis

Zhang, Teng; Zarkower, David

doi:10.1016/j.scr.2017.07.026

Cited by 50 publications

(33 citation statements)

References 57 publications

(90 reference statements)

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“…For example, mice homozygous for a null mutant of EGR1 are sterile, with females having an abnormal development of the ovary (Topilko et al, 1998). Moreover, DM domain-containing transcription factors control sexual differentiation across evolution and have crucial roles in the development of mammalian testis and germline (Kopp, 2012;Zhang and Zarkower, 2017). Given these tantalizing hints and apparent similarities, we suggest that it will be relevant to study whether LIN28 and let-7 control the timing of mammalian sexual organ development through LIN41 and EGR/NAB or DM domain-containing transcription factors.…”

Section: Discussionmentioning

confidence: 99%

let-7controls the transition to adulthood by releasing select transcriptional regulators from repression by LIN41

Aeschimann

Neagu

Rausch

et al. 2018

Preprint

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Development of multicellular organisms relies on faithful temporal control of cell fates. InCaenorhabditis elegans, the heterochronic pathway governs temporal patterning of somatic cells. This function may be phylogenetically conserved as several heterochronic genes have mammalian orthologues, and as the heterochronic let-7 miRNA and its regulator LIN28 appear to time the onset of puberty in mice and humans. Here, we have investigated how let-7 promotes the transition to adulthood in C. elegans. We find that let-7 controls each of three relevant processes, namely male and female sexual organ morphogenesis as well as changes in skin progenitor cell fates, through the same single target, lin-41. LIN41 in turn silences two pairs of targets post-transcriptionally, by binding and silencing their mRNAs. The EGR-type transcription factor LIN-29a and its co-factor, the NAB1/2 orthologous MAB-10, mediate control of progenitor cell fates and vulval integrity. By contrast, male tail development depends on regulation of the DM domain-containing transcription factors DMD-3 and MAB-3. Our results provide mechanistic insight into an exemplary temporal patterning pathway, demonstrate that let-7 -LIN41 function as a versatile regulatory module that can be connected to different outputs, and reveal how several levels of post-transcriptional regulation ultimately achieve effects through controlling transcriptional outputs.

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Section: Discussionmentioning

confidence: 99%

let-7controls the transition to adulthood by releasing select transcriptional regulators from repression by LIN41

Aeschimann

Neagu

Rausch

et al. 2018

Preprint

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“…In foetal ovaries, RA and STRA8 induce the meiotic initiation programme, whereas the entry into meiosis in males is thought to be inhibited by the expression of the CYP26B gene, which encodes a RA‐degrading enzyme. Moreover, a number of important regulatory players have been identified in recent years, including DAZL, FGF9, NANOS2/3 and DMRT1 (Jorgensen et al ., ; Spiller et al ., ; Zhang & Zarkower, ).…”

Section: Meiosis: a Brief Overviewmentioning

confidence: 99%

Meiotic gene activation in somatic and germ cell tumours

Feichtinger

McFarlane

2019

Andrology

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Background Germ cell tumours are uniquely associated with the gametogenic tissues of males and females. A feature of these cancers is that they can express genes that are normally tightly restricted to meiotic cells. This aberrant gene expression has been used as an indicator that these cancer cells are attempting a programmed germ line event, meiotic entry. However, work in non‐germ cell cancers has also indicated that meiotic genes can become aberrantly activated in a wide range of cancer types and indeed provide functions that serve as oncogenic drivers. Here, we review the activation of meiotic factors in cancers and explore commonalities between meiotic gene activation in germ cell and non‐germ cell cancers. Objectives The objectives of this review are to highlight key questions relating to meiotic gene activation in germ cell tumours and to offer possible interpretations as to the biological relevance in this unique cancer type. Materials and Methods PubMed and the GEPIA database were searched for papers in English and for cancer gene expression data, respectively. Results We provide a brief overview of meiotic progression, with a focus on the unique mechanisms of reductional chromosome segregation in meiosis I. We then offer detailed insight into the role of meiotic chromosome regulators in non‐germ cell cancers and extend this to provide an overview of how this might relate to germ cell tumours. Conclusions We propose that meiotic gene activation in germ cell tumours might not indicate an unscheduled attempt to enter a full meiotic programme. Rather, it might simply reflect either aberrant activation of a subset of meiotic genes, with little or no biological relevance, or aberrant activation of a subset of meiotic genes as positive tumour evolutionary/oncogenic drivers. These postulates provide the provocation for further studies in this emerging field.

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“…Although the mechanisms that regulate sexual differentiation appear different between worms, flies, and mice, there are also commonalities. As we have discussed, the DM family of transcription factors plays an important role in sexual differentiation in both worms and flies; intriguingly, the mouse genome contains several loci that code for DM family related transcription factors (DMRTs) [44]. However, the function of these genes in sexual differentiation in mice remains unclear.…”

Section: Future Directionsmentioning

confidence: 99%

Molecular mechanisms underlying sexual differentiation of the nervous system

Knoedler

Shah

2018

Current Opinion in Neurobiology

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A long-standing goal in developmental neuroscience is to understand the mechanisms by which steroid sex hormones pattern the mammalian central nervous system along male or female pathways to enable subsequent displays of sexually dimorphic behaviors. In this article, we review recent advances in understanding the epigenetic and transcriptional mechanisms mediating sexual differentiation of the brain in mammals, flies, and worms. These studies suggest a model of sexual differentiation wherein master regulators of sex determination initiate a cascade of sexually dimorphic gene expression that controls development of neural pathways and behavioral displays in a strikingly modular manner. With these advances in molecular genetics, it is now feasible to disassemble different components of sexually dimorphic social behaviors without disrupting other behavioral interactions. Such experimental tractability promises rapid advances in this exciting field.

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DMRT proteins and coordination of mammalian spermatogenesis

Cited by 50 publications

References 57 publications

let-7controls the transition to adulthood by releasing select transcriptional regulators from repression by LIN41

let-7controls the transition to adulthood by releasing select transcriptional regulators from repression by LIN41

Meiotic gene activation in somatic and germ cell tumours

Molecular mechanisms underlying sexual differentiation of the nervous system

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