🚨 A novel role for microRNAs 👉 they control mammalian sex determination 🧐 Find out in our new pre-print: “Complete male-to-female sex reversal in XY mice lacking the miR-17~92 cluster” https://t.co/zYU5mjp7cg A detailed thread below 🧵

Ever wondered how bats develop wings from their hands? 🦇✨ Check out our new preprint and the thread below! 🤓 👏Big applause to our amazing first authors @M_Schindler_ and @ChrisFeregrino and thanks to all our co-authors for their help! 🥂 https://t.co/9ZzjxzUwnY

PhD position available in my lab - Fully funded! Please, apply or RT! 👩‍🔬🐭🧫

Magnificent stripy eye work from @Alihuma89 and colleagues showing everyone's second favourite gene, Sox9, is needed in the stem cells that maintain the corneal surface. https://t.co/C7JtDouL1h @preLights @the_Node

My thoughts on a landmark paper from @Alihuma89 @Dariloops et al. A brilliant contribution to the field of #sexdetermination opening up many more avenues of research ahead👏 @TheScientistLLC 👇 Deleting a MicroRNA Cluster Reversed Biological Sex in Mice

🧬Identifican un grupo de pequeñas moléculas necesarias para la determinación del sexo en mamíferos. Investigadores del @CABD_UPO_CSIC y la @CanalUGR demuestran por primera vez el papel determinante que juegan los microARNs en este proceso. 👉 https://t.co/kmhjBY1naD

The final version of our article is available We report a novel role for microRNAs in sex determination. A nice collaboration with Barrionuevo and Jimenez lab, and led by @Alihuma89 @IreneMota @Milape42 👏👏 @MDC_Berlin @BIMSB_MDC @CABD_UPO_CSIC https://t.co/UITwrtzAyF

How did skates evolve their characteristics wing-like fins?🧚 Find clues in our last paper @Nature A great team effort w @jjtenagu @rdacemel @Ferdix @tetsuyanakamu @tzinicris_p @elcalmus1 @DanRokhsar Part of the rich legacy of the late @jlgomska https://t.co/Blo70YFQQ3

13/13 In summary, we reveal a novel role for the miR-17~92 cluster and for miRNAs in controlling the early steps of mammalian #sexdetermination. You can find more details in the manuscript. Get in touch with us with any potential question!!

12/13 But this state of sex ambiguity is rapidly resolved towards the female fate, with the initiation of germ cell meiosis, an early sign of ovarian differentiation (OCT4-, SYCP3+)

11/13 SOX9 antagonizes with FOXL2, an ovarian marker. By immunofluorescence, we observe for that FOXL2 is activated in XY mutants shortly after #sexdetermination in SOX9+ cells. This indicates that mutant pre-supporting cells undergo a transient state of sex ambiguity!

10/13 Those effects connect with the initially description of miRNA function as temporal regulators of cell-fate decisions, and which inactivation caused heterochronic shifts in gene expression and differentiation https://t.co/bnwT59hYaY

9/13 This delayed SRY expression affects its downstream target, SOX9, another key factor for Sertoli cell differentiation. SOX9 is transiently expressed in pre-supporting cells, denoting an initial attempt for Sertoli cell differentiation. However, it quickly fades out.

8/13 The delayed Sertoli cell differentiation prompted us to investigate the expression of a key factor for this process: the Y-linked testis-determining factor SRY. IF analyses revealed that SRY is heterochronically expressed, showing a temporal delay in mutant gonads.

7/13 Focusing on deregulated genes, we see that predicted targets are preferentially upregulated in mutants, compared to non-target genes. This suggests that miR-17~92 acts as fine-tuners of gene networks rather than regulating a few genes, also described for other miRNAs

6/13 Despite quickly entering the ovarian program, scRNA-seq analysis revealed that Sertoli cells (a testis-specific cell type) were observed in XY mutants. Yet, their differentiation is delayed in time.

5/13 GO analysis also identified non-sex-related biological processes that are altered in mutants, like cell proliferation. Indeed, miR-17~92 knockout gonads were smaller than controls, suggesting that this cluster regulates normal gonadal growth.

4/13 RNA-seq experiments revealed that mutant gonads acquire a female-like gene expression pattern shortly after sex determination takes place (E11.5 and afterwards)

3/13 Here we demonstrate that XY mouse embryos lacking the miR-17~92 cluster develop as phenotypic females that are indistinguishable from their XX counterparts. They develop ovaries instead of testes!

2/13 miRNAs are small molecules with big implications in developmental and disease. Yet, their potential involvement in #sexdetermination remained elusive.

1/13 But first, a huge thanks to all the people, from Granada to Berlin, who made this work possible @IreneMota, @Milape42, @RealFany, Johanna Jedamzick, Miguel Burgos, @Dariloops, Rafael Jiménez and Paco Barrionuevo