Hif1α is required for Wnt regulated gene expression during Xenopus tropicalis tail regeneration

Regeneration of complex tissues is initiated by an injury-induced stress response, eventually leading to activation of developmental signaling pathways, such as Wnt signaling. How early injury cues are interpreted and coupled to activation of these developmental signals and their targets is not well understood. Here, we show that Hif1α, a stress induced transcription factor, is required for tail regeneration in Xenopus tropicalis. We find that Hif1α is required for regeneration of differentiated axial tissues, including axons and muscle. Using RNA-sequencing, we find that Hif1α and Wnt converge on a broad set of genes required for posterior specification and differentiation, including the posterior hox genes. We further show that Hif1α is required for transcription via a Wnt-responsive element, a function that is conserved in both regeneration and early neural patterning. Our findings indicate a regulatory role for Hif1α in Wnt mediated gene expression across multiple tissue contexts.

The Role of Neurodevelopmental Pathways in Brain Tumors

Disruptions to developmental cell signaling pathways and transcriptional cascades have been implicated in tumor initiation, maintenance and progression. Resurgence of aberrant neurodevelopmental programs in the context of brain tumors highlights the numerous parallels that exist between developmental and oncologic mechanisms. A deeper understanding of how dysregulated developmental factors contribute to brain tumor oncogenesis and disease progression will help to identify potential therapeutic targets for these malignancies. In this review, we summarize the current literature concerning developmental signaling cascades and neurodevelopmentally-regulated transcriptional programs. We also examine their respective contributions towards tumor initiation, maintenance, and progression in both pediatric and adult brain tumors and highlight relevant differentiation therapies and putative candidates for prospective treatments.

Regulation of Drosophila Hematopoiesis in Lymph Gland: From a Developmental Signaling Point of View

The Drosophila hematopoietic system is becoming increasingly attractive for its simple blood cell lineage and its developmental and functional parallels with the vertebrate system. As the dedicated organ for Drosophila larval hematopoiesis, the lymph gland harbors both multipotent stem-like progenitor cells and differentiated blood cells. The balance between progenitor maintenance and differentiation in the lymph gland must be precisely and tightly controlled. Multiple developmental signaling pathways, such as Notch, Hedgehog, and Wnt/Wingless, have been demonstrated to regulate the hematopoietic processes in the lymph gland. Focusing on blood cell maintenance and differentiation, this article summarizes the functions of several classic developmental signaling pathways for lymph gland growth and patterning, highlighting the important roles of developmental signaling during lymph gland development as well as Drosophila larval hematopoiesis.

Regeneration in sponge Sycon ciliatum mimics postlarval development

Somatic cells dissociated from an adult sponge can re-organize and develop into a functional juvenile. However, the extent to which regeneration recapitulates embryonic developmental signaling pathways has remained enigmatic for more than a century. To this end, we have standardized and established a sponge Sycon ciliatum regeneration protocol to achieve consistent regeneration in cell culture. From the morphological analysis, we demonstrated that dissociated sponge cells follow a series of morphological events resembling embryonic and postlarval development. Hence, we propose that sponge regeneration represents somatic development. To support our hypothesis, we performed high-throughput sequencing on regenerating samples and compared the data with regular embryonic and postlarval development of Sycon ciliatum. Our comparative transcriptomic analysis illuminates that sponge regeneration is equally as dynamic as embryogenesis. We find that sponge regeneration is orchestrated by complex regulatory mechanisms by recruiting signaling pathways like those utilized in embryonic development to organize into a functional juvenile. In the current study, we lay down the basic framework to study Sycon ciliatum regeneration. Since sponges are likely to be the first branch of extant multicellular animal and the sister lineage to nearly all animals, we suggest that this system can be explored to study the genetic features underlying the evolution of multicellularity and regeneration.