Edited by: Seppo Vainio and Satu Kuure
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The Spemann-Mangold organiser and the dissemination of its discovery in interwar Finland
Int. J. Dev. Biol. (2024) 68: 149-159
https://doi.org/10.1387/ijdb.240253jn
ABSTRACT
A century has passed since the publication of the discovery of the Spemann-Mangold organiser, most visibly celebrated by the Festschrift Spemann and Mangold centennial special issue in Cells & Development and the conference Self-Organization in Biology: Freiburg Spemann-Mangold Centennial Symposium in September 2024. In honour of the anniversary, the Festschrift commemorates and reviews the history of the Spemann school of embryology and the later developments in the quest to understand the mechanistic underpinnings of the organiser. Here, I share a few new and untold insights from the Finnish archives on how the discovery of the organiser was communicated to and within Finland in the 1920s and ‘30s. The Finnish zoologists Alexander Luther and Gunnar Ekman had been visiting scholars in Spemann’s laboratory, brought the field of experimental embryology to their home country, and incorporated it into the curriculum. Especially Ekman taught embryology to a generation of students in both tertiary and secondary education, created the Finnish terminology of the field, and actively popularised the latest discoveries in various books and journals....OPEN ACCESS
DUX4, the rockstar of embryonic genome activation?
Int. J. Dev. Biol. (2024) 68: 161-168
https://doi.org/10.1387/ijdb.230247sn
ABSTRACT
During the initial days of development, the embryo gradually shifts from reliance on maternally provided RNAs and proteins to regulation of its own development. This transition is marked by embryonic genome activation (EGA). While the factors driving human EGA remain poorly characterized, accumulating evidence suggests that double homeobox 4 (DUX4) is an important regulator of this process. Despite advances in single-cell methods which have allowed studies in early human embryos, fundamental questions regarding the function and regulation of DUX4 persist. Here, we review current knowledge of DUX4 with a focus on EGA in humans.OPEN ACCESS
Enhancer-promoter communication in Drosophila developmental gene transcription
Int. J. Dev. Biol. (2024) 68: 169-188
https://doi.org/10.1387/ijdb.230218gh
ABSTRACT
Enhancers play an essential role in gene regulation by receiving cues from transcription factors and relaying these signals to modulate transcription from target promoters. Enhancer-promoter communications occur across large linear distances of the genome and with high specificity. The molecular mechanisms that underlie enhancer-mediated control of transcription remain unresolved. In this review, we focus on research in Drosophila uncovering the molecular mechanisms governing enhancer-promoter communication and discuss the current understanding of developmental gene regulation. The functions of protein acetylation, pausing of RNA polymerase II, transcriptional bursting, and the formation of nuclear hubs in the induction of tissue-specific programs of transcription during zygotic genome activation are considered.OPEN ACCESS
Genetic targeting of lymphatic endothelial cells in mice: current strategies and future perspectives
Int. J. Dev. Biol. (2024) 68: 189-198
https://doi.org/10.1387/ijdb.230215tm
ABSTRACT
Lymphatic vessels within different organs have diverse developmental origins, depend on different growth factor signaling pathways for their development and maintenance, and display notable tissue-specific adaptations that contribute to their roles in normal physiology and in various diseases. Functional studies on the lymphatic vasculature rely extensively on the use of mouse models that allow selective gene targeting of lymphatic endothelial cells (LECs). Here, we discuss LEC diversity and provide an overview of some of the commonly used LEC-specific inducible Cre lines and induction protocols, outlining essential experimental parameters and their implications. We describe optimized treatment regimens for embryonic, postnatal and adult LECs, efficiently targeting organs that are commonly studied in lymphatic vascular research, such as the mesentery and skin. We further highlight the anticipated outcomes and limitations associated with each induction scheme and mouse line. The proposed protocols serve as recommendations for laboratories initiating studies involving targeting of the lymphatic vasculature, and aim to promote uniformity in lineage tracing and functional studies...OPEN ACCESS
Epigenetic and transcriptional regulation of neuron phenotype
Int. J. Dev. Biol. (2024) 68: 199-209
https://doi.org/10.1387/ijdb.230204ka
ABSTRACT
Understanding the structure and function of cells is central to cell biology and physiology. The ability to control cell function may benefit biomedicine, such as cell-replacement therapy or regeneration. If structure defines function and cells are composed of water, lipids, small metabolites, nucleic acids, and proteins, of which the latter are largely encoded by the DNA present in the same cell, then one may assume that the cell types and variation in cellular phenotypes are shaped by differential gene expression. Cells of the same cell type maintain a similar composition. In this review, I will discuss the epigenetic and transcription regulation mechanisms guiding cell fate- specific gene expression in developing neural cells. Differentiation involves processes of cell-fate selection, commitment and maturation, which are not necessarily coupled.OPEN ACCESS
Fgf8 gene regulatory network and the isthmic organizer: an evolutionary perspective
Int. J. Dev. Biol. (2024) 68: 211-222
https://doi.org/10.1387/ijdb.240198ah
ABSTRACT
The midbrain-hindbrain boundary (MHB), also known as the isthmic organizer (IsO), plays a critical role in the developmental patterning of the posterior midbrain and anterior hindbrain. Understanding the wiring of this organizer’s deeply conserved gene regulatory network is of significant interest for both evolutionary and neurodevelopmental biology. Various secreted signalling molecules and transcription factors have been identified as being important components for the formation and function of the MHB. Among these, FGF8 is considered a primary mediator of IsO activity; it directs anterior-posterior patterning and promotes the specification and maintenance of the MHB. While the core gene regulatory network governing MHB development is well-characterized, the direct interactions between key regulatory genes and the cis-regulatory elements that control their spatiotemporal expression remain poorly understood. This review summarizes the current knowledge of the gene regulatory network underlying the formation of the vertebrate midbrain-hindbrain boundary. We focus in particular on Fgf8 and its regulatory landscape from an evolutionary perspective.OPEN ACCESS
The GLI code controls HNF1A levels during foregut differentiation
Int. J. Dev. Biol. (2024) 68: 223-230
https://doi.org/10.1387/ijdb.230220lg
ABSTRACT
Differentiation of human induced pluripotent stem cells towards pancreatic islet endocrine cells is a complex process, involving the stepwise modulation of key developmental pathways, such as the Hedgehog signaling inhibition during early differentiation stages. In tandem with this active inhibition, key transcription factors for the islet endocrine cell fate, such as HNF1A, show specific changes in their expression patterns. Here we designed a pilot study aimed at investigating the potential interconnection between HH-signaling inhibition and the increase in the HNF1A expression during early regeneration, by inducing changes in the GLI code. This unveiled a link between the two, where GLI3-R mediated Hedgehog target genes inhibition is apparently required for HNF1A efficient expression.OPEN ACCESS
Wnt target gene Ascl4 is dispensable for skin appendage development
Int. J. Dev. Biol. (2024) 68: 231-239
https://doi.org/10.1387/ijdb.240007vp
ABSTRACT
The development of skin appendages, including hair follicles, teeth and mammary glands is initiated through the formation of the placode, a local thickening of the epithelium. The Wnt/β-catenin signaling cascade is an evolutionary conserved pathway with an essential role in placode morphogenesis, but its downstream targets and their exact functions remain ill defined. In this study, we identify Achaete-scute complex-like 4 (Ascl4) as a novel target of the Wnt/β-catenin pathway and demonstrate its expression pattern in the signaling centers of developing hair follicles and teeth. Ascl transcription factors belong to the superfamily of basic helix-loop-helix transcriptional regulators involved in cell fate determination in many tissues. However, their specific role in the developing skin remains largely unknown. We report that Ascl4 null mice have no overt phenotype. Absence of Ascl4 did not impair hair follicle morphogenesis or hair shaft formation suggesting that it is non-essential for hair follicle development. No tooth or mammary gland abnormalities were detected either. We suggest that other transcription factors may functionally compensate for the...OPEN ACCESS
Int. J. Dev. Biol. (2024) 68: 241-249
https://doi.org/10.1387/ijdb.230211na
ABSTRACT
Wnt4 signaling is critical for mammalian female sex determination, in female reproductive organ development, in follicular and oocyte maturation, and in steroid hormone production. When Wnt4 function is impaired, female embryos undergo partial female to male sex-reversal. This phenotype is associated with the expression of a set of somatic genes that are typical for the male differentiation pathways such as those of the Leydig cells. Given the roles of the 3`untranslated region (3`UTR) in control of gene expression, we addressed whether a knock-in of a stop cassette to 3`END of the Wnt4 gene would impact female reproductive system development or function. The 3`UTRstop cassette indeed affected Wnt4 gene expression in vivo so that the respective mRNA was upregulated in the ovaries of a three month-old female. The homozygous Wnt4 3`UTRstop mice were noted to be leaner than their wild type (WT) littermate controls. Analysis of the ovarian follicular count at the age of three months revealed increased pre-antral but reduced ovarian corpus luteum follicular counts. Furthermore, two out of five of the...OPEN ACCESS
Ccer1 is a spermatid-specific gene required for spermatogenesis and male fertility
Int. J. Dev. Biol. (2024) 68: 251-262
https://doi.org/10.1387/ijdb.240205rp
ABSTRACT
Male infertility is a multifactorial condition for which the underlying causes frequently remain undefined. Genetic factors have long been associated with male fertility. However, many of them are poorly or not at all characterized and their biological functions are unknown. Identifying the key genes behind male infertility is crucial for improving prognosis and treatment options, as well as for evaluating the risk of passing on genetic defects through natural or assisted reproductive methods to the next generation. Here, we have studied the Coiled-coil domain-containing glutamate-rich protein 1 (Ccer1), a poorly characterized gene specific to vertebrates. We demonstrate that it is enriched during spermiogenesis in spermatids in both mice and humans. The studied Ccer1 knockout mice exhibit significant subfertility due to the absence of Ccer1 function, which leads to altered sperm head and tail ultrastructure. This study defines Ccer1 as a spermatid-specific gene critical for spermiogenesis, suggesting it would be worthwhile inspecting when there is a suspicion of male infertility associated with genetic causes.
