During my university studies in Munich, Germany, I explored Zoology, Biochemistry, Parasitology, and Immunology to focus on tumor biology and melanoma formation in my Diploma and PhD projects in Judy Johnson's lab. She encouraged, guided, and provided maximal freedom for scientific thinking and all basic methods.

Cell specification and the plasticity of cell fate in response to surrounding signals and the resulting precise gene activation/repression mechanisms remain my strong interest. At the end of my PhD I came to three major conclusions: first, we cannot fully understand a pathological situation without knowing in depth about the normal genesis of cells along development; second, we need to study molecular mechanisms in vivo to avoid cell lineage artifacts; and third, we need to simplify things by using less complex but informative model organisms that can reveal evolutionarily conserved concepts.

For my post-doc, I chose Xenopus as an in vivo model at UC Irvine (Prof. Ken Cho lab) and Caltech Pasadena (Prof. Scott Fraser lab) to reveal conserved molecular players in embryonic signaling, notably that both Drosophila and Xenopus Dishevelled (Dsh) can mediate Wnt signaling in Xenopus secondary axis (Spemann's Organizer) formation (Rothbächer et al., 1995; Rothbächer et al., 2000). We also showed that non-canonical planar cell polarity signaling via Dsh controls gastrulation in vertebrates (Wallingford et al., 2000) while the canonical ß-catenin from Hydra could induce complete secondary axes upon mRNA injection in Xenopus embryos (Hobmayer et al., 2000).

During my postdoc time, my daughter was born and taught me the true miracles of life, also straightening out my priorities and my efficiency. Together, we thereafter moved to Marseille, France.

At that time tunicates (ascidians) were being established in Patrick Lemaire's lab at the Marseille Institute of Developmental Biology as a simpler chordate developmental model, and I soon realized that ascidians could give access to many questions that were rather difficult to address in Xenopus. As invertebrate chordates, their larvae resemble an evolutionary prototype for vertebrates! Transparency, few and large cells, and an invariant developmental lineage seemed truly amazing, in addition to techniques like electroporation en masse to allow for functional genomics in synchronized embryos. Here, I learned and co-developed many tools for Ciona functional genomics and I worked in collaboration with this lab for around 10 years while publishing my independent research work. Here, I also obtained the “habilitation to direct research” and supervised doctoral candidates. Discovering the earliest zygotic events and the regulatory DNA (enhancer) level of maternally activated target genes was my main interest in ascidians, and we revealed for example, that a GATA factor is required to specify ectodermal cells, and its range of action is restricted by ß-catenin (Rothbächer et al., 2007).

In 2012, I established an independent tunicate research group at the University of Innsbruck, Austria. I have a high teaching load but enjoy mentoring young researchers, and also encourage them to develop new experimental approaches in Ciona (Kari et al., 2016). We continued studying the repressive mechanism of ß-catenin on GATA (Oda-Ishii et al., 2016), which is reminiscent of opposite wnt/ß-catenin signaling in C. elegans (Murgan et al., 2015). In parallel, inspired by neighboring groups and the technical possibilities offered by Ciona, I designed a new project aimed at using our knowledge of bioadhesion in ascidians to develop biomimetic glues (Davey et al., 2021). Primarly conducted by a female reseacher, Fan Zeng, first as a Ph.D. student and currently as a postdoc in my lab (Figure 1), we described in detail the cells within the Ciona sensory adhesive papillae (Figure 2a,b; Zeng, Wunderer, Salvenmoser, Ederth, et al., 2019) as well as adhesive components and markers of the adhesive material that these cells secrete at the time of larval settlement (Zeng, Wunderer, Salvenmoser, Hess, et al., 2019), and collaborated with another group on the specification of papillar cells (Johnson et al., 2023). Presently, we are determining the molecular composition of the larval glue in three ascidians and performed Phallusia long-read genome sequencing to resolve repeated regions (unpublished). Through novel CRISPR technology, Ph.D. candidate Alessandro Pennati (Figure 1) identified and characterized conserved cis-regulation of tail sensory neuron genes (Figure 2c,d) (Papadogiannis et al., 2022). He is now working on an additional repressive mechanism that further refines binary cell fate choice. Sadly, our work on ascidians is increasingly affected by the warming seas, notably by a seemingly shortened reproductive season in both the Northern Altlantic and the Mediterranean Sea.

在德国慕尼黑大学学习期间，我在朱迪·约翰逊实验室的文凭和博士项目中探索了动物学、生物化学、寄生虫学和免疫学，重点研究肿瘤生物学和黑色素瘤形成。她鼓励、指导并为科学思维和一切基本方法提供最大的自由。

细胞特化和细胞命运响应周围信号的可塑性以及由此产生的精确基因激活/抑制机制仍然是我的强烈兴趣。在博士学位结束时，我得出了三个主要结论：首先，如果不深入了解细胞发育过程中的正常发生，我们就无法完全理解病理情况；其次，我们需要研究体内分子机制，以避免细胞谱系伪影；第三，我们需要使用不太复杂但信息丰富的模型生物来简化事情，这些模型生物可以揭示进化上保守的概念。

对于我的博士后，我选择了加州大学欧文分校（Ken Cho 教授实验室）和加州理工学院帕萨迪纳分校（Scott Fraser 教授实验室）的非洲爪蟾作为体内模型，以揭示胚胎信号传导中保守的分子参与者，特别是果蝇和非洲爪蟾都蓬乱(Dsh) 可以介导非洲爪蟾第二轴（Spemann's Organizer）形成中的 Wnt 信号传导（Rothbächer 等，  1995；Rothbächer 等，  2000）。我们还表明，通过 Dsh 的非经典平面细胞极性信号控制脊椎动物的原肠胚形成（Wallingford 等人，  2000），而来自水螅的经典 ß-catenin 可以在非洲爪蟾胚胎中注射 mRNA 时诱导完整的次轴（Hobmayer 等人，2000）。  2000）。

在我博士后期间，我的女儿出生了，她教会了我生命的真正奇迹，也理清了我的优先事项和效率。此后，我们一起搬到了法国马赛。

当时，马赛发育生物学研究所的 Patrick Lemaire 实验室正在建立被囊动物（海鞘动物）作为一种更简单的脊索动物发育模型，我很快意识到海鞘动物可以解决许多在非洲爪蟾中很难解决的问题。作为无脊椎动物脊索动物，它们的幼虫类似于脊椎动物的进化原型！除了诸如集体电穿孔之类的允许在同步胚胎中进行功能基因组学的技术之外，透明度、少量而大的细胞以及不变的发育谱系似乎确实令人惊叹。在这里，我学习并共同开发了许多Ciona功能基因组学工具，我与该实验室合作了大约 10 年，同时发表了我的独立研究工作。在这里，我还获得了“指导研究资格”并指导了博士生。发现最早的合子事件和母体激活的靶基因的调节 DNA（增强子）水平是我对海鞘的主要兴趣，例如，我们发现需要 GATA 因子来指定外胚层细胞，并且其作用范围受到以下因素的限制： β-连环蛋白（Rothbächer 等，  2007）。

2012年，我在奥地利因斯布鲁克大学建立了一个独立的被囊类研究小组。我的教学负担很大，但喜欢指导年轻的研究人员，并鼓励他们在Ciona中开发新的实验方法（Kari 等人，  2016）。我们继续研究 ß-catenin 对 GATA 的抑制机制（Oda-Ishii et al.,  2016），这让人想起秀丽隐杆线虫中相反的 wnt/ß-catenin 信号传导（Murgan et al.,  2015）。与此同时，受到邻近团体和Ciona提供的技术可能性的启发，我设计了一个新项目，旨在利用我们在海鞘生物粘附方面的知识来开发仿生胶（Davey 等人，  2021）。主要由一位女性研究员范曾（Fan Zeng）主持，她最初是一名博士。作为我实验室的学生和目前的博士后（图 1），我们详细描述了Ciona感觉粘着乳头内的细胞（图 2a、b；Zeng、Wunderer、Salvenmoser、Ederth 等，2019）以及粘着剂研究人员对这些细胞在幼虫定居时分泌的粘附材料的成分和标记进行了研究（Zeng、Wunderer、Salvenmoser、Hess 等人，  2019），并与另一个小组合作研究乳头细胞的规格（Johnson 等人，  2023）。目前，我们正在确定三种海鞘幼虫胶的分子组成，并进行阴茎体长读基因组测序以解析重复区域（未发表）。通过新颖的 CRISPR 技术，博士。候选人 Alessandro Pennati（图 1）鉴定并表征了尾部感觉神经元基因的保守顺式调节（图 2c、d）（Papadogiannis 等人，  2022）。他现在正在研究一种额外的抑制机制，进一步完善二元细胞命运选择。遗憾的是，我们对海鞘的研究越来越受到海洋变暖的影响，特别是北大西洋和地中海繁殖季节似乎缩短的影响。