Transcription factor EB (TFEB) function in Xenopus neural crest

CERVINO, AILEN; DIEGO MARTÍN JOFRÉ; DANIEL HOCHBAUM; CIRIO, MARIA CECILIA

Congreso; Latin American Society for Developmental Biology - LASDB; 2019

The transcription factor EB (TFEB) plays a central role in the regulation of basic cellular processes, such as lysosomal biogenesis and autophagy regulating important developmental and differentiation events. While the role of other family members such as MITF, have been extensively characterized in development; the embryonic lethality of TFEB-null mice has precluded a characterization of TFEB function during embryogenesis. To investigate the effects of Tfeb depletion during embryonic development we performed loss of function studies using a specific antisense morpholino in Xenopus laevis. Since a requirement of the other MiT family members for development of neural crest-derived pigmented cells, osteoblasts and mast cells has been described, we decided to investigate a role of Tfeb in neural crest (NC) development. Knock-down of tfeb results in reduced expression of the NC specifier gene twist in pre-migratory NC cells and defective NC migration. Further, we investigated the effect of tfeb knockout on NC derivatives and found that cranial cartilage morphology was affected showing reduction of the size and abnormal head shape. Interestingly, similar to what was described for MITF knock-out mice, Tfeb-depleted Xenopus embryos have abnormally small eyes (microphthalamia). Our results show that Tfeb has a role in NC cells and cranofacial development and suggest a possible participation of lysosomal biogenesis and/or autophagy in these processes.