Functions of peroxisome proliferator-activated receptors (PPAR) in skin homeostasis

The peroxisome proliferator-activated receptors (PPAR) are ligand-activated transcription factors that belong to the nuclear hormone receptor family. Three isotypes (PPARα, PPARβ or δ, and PPARγ) with distinct tissue distributions and cellular functions have been found in vertebrates. All three PPAR isotypes are expressed in rodent and human skin. They were initially investigated for a possible function in the establishment of the permeability barrier in skin because of their known function in lipid metabolism in other cell types. In vitro studies using specific PPAR agonists and in vivo gene disruption approaches in mice indeed suggest an important contribution of PPARα in the formation of the epidermal barrier and in sebocyte differentiation. The PPARγ isotype plays a role in stimulating sebocyte development and lipogenesis, but does not appear to contribute to epidermal tissue differentiation. The third isotype, PPARβ, regulates the late stages of sebaceous cell differentiation, and is the most effective isotype in stimulating lipid production in these cells, both in rodents and in humans. In addition, PPARβ activation has pro-differentiating effects in kera-tinocytes under normal and inflammatory conditions. Finally, preliminary studies also point to a potential role of PPAR in hair follicle growth and in melanocyte differentiation. By their diverse biological effects on cell proliferation and differentiation in the skin, PPAR agonists or antagonists may offer interesting oppotunities for the treatment of various skin disorders characterized by inflammation, cell hyperproliferation, and aberrant differentiatio

Heterochronic Developmental Shifts Underlying Squamate Cerebellar Diversity Unveil the Key Features of Amniote Cerebellogenesis

Despite a remarkable conservation of architecture and function, the cerebellum of vertebrates shows extensive variation in morphology, size, and foliation pattern. These features make this brain subdivision a powerful model to investigate the evolutionary developmental mechanisms underlying neuroanatomical complexity both within and between anamniote and amniote species. Here, we fill a major evolutionary gap by characterizing the developing cerebellum in two non-avian reptile species—bearded dragon lizard and African house snake—representative of extreme cerebellar morphologies and neuronal arrangement patterns found in squamates. Our data suggest that developmental strategies regarded as exclusive hallmark of birds and mammals, including transit amplification in an external granule layer (EGL) and Sonic hedgehog expression by underlying Purkinje cells (PCs), contribute to squamate cerebellogenesis independently from foliation pattern. Furthermore, direct comparison of our models suggests the key importance of spatiotemporal patterning and dynamic interaction between granule cells and PCs in defining cortical organization. Especially, the observed heterochronic shifts in early cerebellogenesis events, including upper rhombic lip progenitor activity and EGL maintenance, are strongly expected to affect the dynamics of molecular interaction between neuronal cell types in snakes. Altogether, these findings help clarifying some of the morphogenetic and molecular underpinnings of amniote cerebellar corticogenesis, but also suggest new potential molecular mechanisms underlying cerebellar complexity in squamates. Furthermore, squamate models analyzed here are revealed as key animal models to further understand mechanisms of brain organization.Peer reviewe

Changes in Hox genes' structure and function during the evolution of the squamate body plan

Hox genes are central to the specification of structures along the anterior-posterior body axis, and modifications in their expression have paralleled the emergence of diversity in vertebrate body plans. Here we describe the genomic organization of Hox clusters in different reptiles and show that squamates have accumulated unusually large numbers of transposable elements at these loci, reflecting extensive genomic rearrangements of coding and non-coding regulatory regions. Comparative expression analyses between two species showing different axial skeletons, the corn snake and the whiptail lizard, revealed major alterations in Hox13 and Hox10 expression features during snake somitogenesis, in line with the expansion of both caudal and thoracic regions. Variations in both protein sequences and regulatory modalities of posterior Hox genes suggest how this genetic system has dealt with its intrinsic collinear constraint to accompany the substantial morphological radiation observed in this group

Shared and differential features of Robo3 expression pattern in amniotes

In Bilaterians, commissural neurons project their axons across the midline of the nervous system to target neurons on the opposite side. In mammals, midline crossing at the level of the hindbrain and spinal cord requires the Robo3 receptor which is transiently expressed by all commissural neurons. Unlike other Robo receptors, mammalian Robo3 receptors do not bind Slit ligands and promote midline crossing. Surprisingly, not much is known about Robo3 distribution and mechanism of action in other vertebrate species. Here, we have use whole-mount immunostaining, tissue clearing and light-sheet fluorescent microscopy to study Robo3 expression pattern in multiple embryonic tissue from diverse representatives of amniotes at distinct stages, including squamate (African house snake), birds (chicken, duck, pigeon, ostrich, emu and zebra finch), early postnatal marsupial mammals (fat-tailed dunnart), and eutherian mammals (mouse and human). The analysis of this rich and unique repertoire of amniote specimen reveals conserved features of Robo3 expression in midbrain, hindbrain and spinal cord commissural circuits, which together with subtle but meaningful modifications could account for species-specific evolution of sensory-motor and cognitive capacities. Our results also highlight important differences of precerebellar nuclei development across amniotes. This article is protected by copyright. All rights reserved

The SmARTR pipeline: A modular workflow for the cinematic rendering of 3D scientific imaging data

Summary: Advancements in noninvasive surface and internal imaging techniques, along with computational methods, have revolutionized 3D visualization of organismal morphology—enhancing research, medical anatomical analysis, and facilitating the preservation and digital archiving of scientific specimens. We introduce the SmARTR pipeline (Small Animal Realistic Three-dimensional Rendering), a comprehensive workflow integrating wet lab procedures, 3D data acquisition, and processing to produce photorealistic scientific data through 3D cinematic rendering. This versatile pipeline supports multiscale visualizations—from tissue-level to whole-organism details across diverse living organisms—and is adaptable to various imaging sources. Its modular design and customizable rendering scenarios, enabled by the global illumination modeling and programming modules available in the free MeVisLab software and seamlessly integrated into detailed SmARTR networks, make it a powerful tool for 3D data analysis. Accessible to a broad audience, the SmARTR pipeline serves as a valuable resource across multiple life science research fields and for education, diagnosis, outreach, and artistic endeavors

Comparative analysis of squamate brains unveils multi-level variation in cerebellar architecture associated with locomotor specialization

AbstractEcomorphological studies evaluating the impact of environmental and biological factors on the brain have so far focused on morphology or size measurements, and the ecological relevance of potential multi-level variations in brain architecture remains unclear in vertebrates. Here, we exploit the extraordinary ecomorphological diversity of squamates to assess brain phenotypic diversification with respect to locomotor specialization, by integrating single-cell distribution and transcriptomic data along with geometric morphometric, phylogenetic, and volumetric analysis of high-definition 3D models. We reveal significant changes in cerebellar shape and size as well as alternative spatial layouts of cortical neurons and dynamic gene expression that all correlate with locomotor behaviours. These findings show that locomotor mode is a strong predictor of cerebellar structure and pattern, suggesting that major behavioural transitions in squamates are evolutionarily correlated with mosaic brain changes. Furthermore, our study amplifies the concept of ‘cerebrotype’, initially proposed for vertebrate brain proportions, towards additional shape characters.</jats:p