TY - JOUR AB - Pancreas organogenesis is a highly dynamic process where neighboring tissue interactions lead to dynamic changes in gene regulatory networks that orchestrate endocrine, exocrine, and ductal lineage formation. To understand the spatio-temporal regulatory logic we have used the Forkhead transcription factor Foxa2-Venus fusion (FVF) knock-in reporter mouse to separate the FVF+ pancreatic epithelium from the FVF− surrounding tissue (mesenchyme, neurons, blood, and blood vessels) to perform a genome-wide mRNA expression profiling at embryonic days (E) 12.5–15.5. Annotating genes and molecular processes suggest that FVF marks endoderm-derived multipotent epithelial progenitors at several lineage restriction steps, when the bulk of endocrine, exocrine and ductal cells are formed during the secondary transition. In the pancreatic epithelial compartment, we identified most known endocrine and exocrine lineage determining factors and diabetes-associated genes, but also unknown genes with spatio-temporal regulated pancreatic expression. In the non-endoderm-derived compartment, we identified many well-described regulatory genes that are not yet functionally annotated in pancreas development, emphasizing that neighboring tissue interactions are still ill defined. Pancreatic expression of over 635 genes was analyzed with the mRNA in situ hybridization Genepaint public database. This validated the quality of the profiling data set and identified hundreds of genes with spatially restricted expression patterns in the pancreas. Some of these genes are also targeted by pancreatic transcription factors and show active chromatin marks in human islets of Langerhans. Thus, with the highest spatio-temporal resolution of a global gene expression profile during the secondary transition, our study enables to shed light on neighboring tissue interactions, developmental timing and diabetes gene regulation. AU - Willmann, S. AU - Müller, N.S. AU - Engert, S. AU - Sterr, M. AU - Burtscher, I. AU - Raducanu, A. AU - Irmler, M. AU - Beckers, J. AU - Sass, S. AU - Theis, F.J. AU - Lickert, H. C1 - 47455 C2 - 39320 CY - Amsterdam SP - 51-64 TI - The global gene expression profile of the secondary transition during pancreatic development. JO - Mech. Dev. VL - 139 PB - Elsevier Science Bv PY - 2016 SN - 0925-4773 ER - TY - JOUR AB - Unveiling mechanisms driving specification, recruitment and regeneration of melanophores is key in understanding melanin-related disorders. This study reports on the applicability of a hybrid focus optoacoustic microscope (HFOAM) for volumetric tracking of migratory melanophores in developing zebrafish. The excellent contrast from highly-absorbing melanin provided by the method is shown to be ideal for label-free dynamic visualization of melanophores in their unperturbed environment. We established safe laser energy levels that enable high-contrast longitudinal tracking of the cells over an extended period of developmental time without causing cell toxicity or pigment bleaching. Owing to its hybrid optical and acoustic resolution, the new imaging technique can be seamlessly applied for noninvasive studies of both optically-transparent larval as well as adult stages of the zebrafish model organism, which is not possible using other optical microscopy methods. AU - Kneipp, M. AU - Estrada, H. AU - Lauri, A. AU - Turner, J.E. AU - Ntziachristos, V. AU - Westmeyer, G.G. AU - Razansky, D. C1 - 46930 C2 - 39062 SP - 300-304 TI - Volumetric tracking of migratory melanophores during zebrafish development by optoacoustic microscopy. JO - Mech. Dev. VL - 138 PY - 2015 SN - 0925-4773 ER - TY - JOUR AB - Sonic hedgehog (Shh) is well known as the molecule responsible for the induction and maintenance of ventral neural tube structures. Recent data have shown that ventral neuronal populations react differentially to the amount of this morphogen not only in the spinal cord, but also in more rostral parts of the brain, like the midbrain. A dorsal expansion in the Shh expression domain modifies the differentiation program in this territory. The lack of Shh produces alterations in the development of this area as well. Here, for the first time, we analyze in detail the development of the different mesencephalic basal nuclei in the absence of Shh. We report that the oculomotor complex is lost, the dopaminergic populations are strongly affected but the red nucleus is maintained. These results point out that not all the midbrain neuronal populations are dependent on Shh for their maintenance, as previously thought. Based on our results and recently published data, we suggest the existence of a specific genetic pathway for the specification of the mesencephalic red nucleus. Foxa2 could be the candidate gene that might control this genetic pathway. AU - Perez-Balaguer, A.* AU - Puelles, E.* AU - Wurst, W. AU - Martinez, S.* C1 - 1025 C2 - 26270 SP - 301-313 TI - Shh dependent and independent maintenance of basal midbrain. JO - Mech. Dev. VL - 126 IS - 5-6 PB - Elsevier Science Bv PY - 2009 SN - 0925-4773 ER - TY - JOUR AU - Schroeder, T. AU - Meier-Stiegen, F.* AU - Schwanbeck, R.* AU - Eilken, H.M. AU - Nishikawa, S.* AU - Häsler, R.* AU - Schreiber, S.* AU - Bornkamm, G.W. AU - Nishikawa, S.-I.* AU - Just, U. C1 - 4438 C2 - 23774 SP - 570-579 TI - Activated Notch1 alters differentiation of embryonic stem cells into mesodermal cell lineages at multiple stages of development. JO - Mech. Dev. VL - 123 PY - 2006 SN - 0925-4773 ER - TY - JOUR AU - Bellipanni, G.* AU - Rink, E.* AU - Bally-Cuif, L. C1 - 10003 C2 - 22571 SP - 215-220 TI - Cloning of two tryptophan hydroxylase genes expressed in the diencephalon of the developing zebrafish brain. JO - Mech. Dev. VL - 119 PY - 2002 SN - 0925-4773 ER - TY - JOUR AU - Pelletier, I. AU - Bally-Cuif, L. AU - Ziegler, I. C1 - 21746 C2 - 19941 SP - 99-103 TI - Cloning and developmental expression of zebrafish GTP cyclohydrolase I. JO - Mech. Dev. VL - 109 PY - 2001 SN - 0925-4773 ER - TY - JOUR AU - Vetter, K.* AU - Wurst, W. C1 - 2785 C2 - 22817 SP - 123-125 TI - Expression of a novel mouse gene 'mbFZb' in distinct regions of the developing nervous system and the adult brain. JO - Mech. Dev. VL - 100 PY - 2001 SN - 0925-4773 ER - TY - JOUR AB - The Delta1 gene encodes one of the Notch ligands in mice. Delta1 is expressed during early embryogenesis in a complex and dynamic pattern in the paraxial mesoderm and neuroectoderm, and is essential for normal somitogenesis and neuronal differentiation. Molecular components thought to act in response to ligand binding and Notch activation have been identified in different species. In contrast, little is known about the transcriptional regulation of Notch receptors and their ligands. As a first step to identify upstream factors regulating Delta1 expression in different tissues, we searched for cis-regulatory regions in the Delta1 promoter able to direct heterologous gene expression in a tissue specific manner in transgenic mice. Our results show that a 4.3 kb genomic DNA fragment of the Delta1 gene is sufficient in a lacZ reporter transgene to reproduce most aspects of Delta1 expression from the primitive streak stage to early organogenesis. Using a minimal Delta1 promoter we also show that this upstream region contains distinct regulatory modules that individually direct tissue-specific transgene expression in subdomains of the endogenous expression pattern. It appears that expression in the paraxial mesoderm depends on the interaction of multiple positive and negative regulatory elements. We also find that at least some regulatory sequences required for transgene expression in subdomains of the neural tube have been maintained during the evolution of mammals and teleost fish, suggesting that part of the regulatory network that controls expression of Delta genes may be conserved. AU - Beckers, J. AU - Caron, A.* AU - Hrabě de Angelis, M. AU - Hans, S.* AU - Campos-Ortega, J.A.* AU - Gossler, A.* C1 - 22301 C2 - 21107 SP - 23-34 TI - Distinct regulatory elements direct Delta1 expression in the nervous system and paraxial mesoderm of transgenic mice. JO - Mech. Dev. VL - 95 PY - 2000 SN - 0925-4773 ER - TY - JOUR AB - Rib-vertebrae (rv) is an autosomal recessive mutation in mouse that affects the morphogenesis of the vertebral column. Axial skeleton defects vary along the anterior-posterior body axis, and include split vertebrae and neural arches, and fusions of adjacent segments. Here, we show that defective somite patterning underlies the vertebral malformations and altered Notch signaling may contribute to the phenotype. Somites in affected regions are irregular in size and shape, epithelial morphology is disrupted, and anterior-posterior somite patterning is abnormal, reminiscent of somite defects obtained in loss-of-function alleles of Notch signaling pathway components. Expression of Dll1, Dll3, Lfng and Notch1 is altered in rv mutant embryos, and rv and Dll1lacZ, a null allele of the Notch ligand Delta1, genetically interact. Mice double heterozygous for rv and Dll1lacZ, show vertebral defects, and one copy of Dll1lacZ on the homozygous rv background enhances the mutant phenotype and is lethal in the majority of cases. However, fine genetic mapping places rv into an interval on chromosome seven that does not contain a gene encoding a known component of the Notch signaling pathway. AU - Beckers, J. AU - Schlautmann, N.* AU - Gossler, A.* C1 - 22303 C2 - 21109 SP - 35-46 TI - The mouse rib-vertebrae mutation disrupts anterior-posterior somite patterning and genetically interacts with a Delta1 null allele. JO - Mech. Dev. VL - 95 PY - 2000 SN - 0925-4773 ER - TY - JOUR AU - Zarbalis, K.* AU - Wurst, W. C1 - 2784 C2 - 22821 SP - 165-168 TI - Expression domains of murine ephrin-A5 in the pituitary and hypothalamus. JO - Mech. Dev. VL - 93 PY - 2000 SN - 0925-4773 ER - TY - JOUR AU - Beckers, J. AU - Clark, A.* AU - Wünsch, K. AU - Hrabě de Angelis, M. AU - Gossler, A.* C1 - 22302 C2 - 21108 SP - 165-168 TI - Expression of the mouse Delta1 gene during organogenesis and fetal development. JO - Mech. Dev. VL - 84 PY - 1999 SN - 0925-4773 ER - TY - JOUR AU - Morrison, A.* AU - Hodgetts, C.* AU - Gossler, A.* AU - Hrabě de Angelis, M. AU - Lewis, J.* C1 - 22325 C2 - 21152 SP - 169-172 TI - Expression of Delta1 and Serrate1 (Jagged1) in the mouse inner ear. JO - Mech. Dev. VL - 84 PY - 1999 SN - 0925-4773 ER -