Myocardin-related transcription factors regulate F-actin organization during gastrulation and neural tube closure in Xenopus embryos

Myocardin-related transcription factors (Mrtfa and Mrtfb), also known as megakaryoblastic leukemia (Mkl1/MAL and Mkl2), associate with serum response factor (Srf) to regulate transcription in response to actin dynamics, however, the functions of Mrtfs in early development are poorly characterized. In this study, we assessed functional roles of Mrtfs in Xenopus embryos. Modulation of Mrtf-dependent transcription in gain- and loss-of-function experiments caused gastrulation and neural tube closure defects, indicating an essential function of Mrtfs in morphogenesis. Notably, both activation and inhibition of Mrtf activity had similar morphological phenotypes. However, dominant interfering Mrtf construct reduced overall F-actin levels, whereas a constitutively active Mrtf construct specifically disrupted F-actin accumulation at the tricellular junctions. Both Mrtf constructs inhibited elongation of ectodermal explants in response to activin, but did not affect RhoA-dependent apical constriction. RNA sequencing of ectoderm with manipulated Mrtf levels confirmed already known Mrtf target genes encoding actins and actin-binding proteins and revealed new Srf-dependent or -independent putative targets. Our findings highlight the importance of Mrtfs in early morphogenetic processes and elucidate their potential targets. Overall design: Stage 11 X. Laevis animal caps injected with mRNA encoding deltaN-MRTF, deltaNSRF-MRTF, DeltaNSAP-MRTF