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Genetic control of akeletal muscle hypertrophy

AuthorsVicente García, Cristina; López-Mayorga, Macarena ; Escudero, Luis M. ; Carvajal, Jaime J.
Issue Date23-Oct-2019
CitationEuropean Developmental Biology Congress (2019)
AbstractThe myogenic regulatory factors (MRFs) Myf5, Mrf4, MyoD and MyoG are transcription factors that control the determination, specification and differentiation of skeletal muscle during development. Mrf4 specific functions remain elusive to date in spite of the three knock-out (KO) models available for over two decades. This can be explained by the disparity in their phenotypes, which ranges from complete lethality at birth to full viability into the adult. By studying the long-range interactions established in the locus, we show that the selectable marker cassette introduced upon generation of the mutants completely sequesters the neighbouring Myf5 promoter, only 8.7 Kb apart. Thus, these models behave phenotypically as partial or full compound Mrf4/Myf5 mutants, obscuring Mrf4 function. Using CRISPR/Cas9 technology, we created two novel KO alleles that do not affect Myf5 expression in cis. Preliminary analyses reveal that the expression patterns of the other MRFs are not affected during development and that, unlike previous KO models, no skeletal defects are observed unless Myf5 is additionally inactivated. Mrf4 KO animals show fibre hypertrophy and, surprisingly, cardiac hypertrophy even if none of the MRFs is ever expressed in the heart. Deep morphologic and transcriptomic characterization of the novel KOs under the paradigms of muscle regeneration, natural hypertrophy and denervation-induced atrophy will shed some light into how Mrf4 controls muscle growth and homeostasis.
DescriptionResumen del trabajo presentado en el European Developmental Biology Congress, celebrado en Alicante (España), del 23 al 26 de octubre de 2019
Appears in Collections:(CABD) Comunicaciones congresos
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