Maria Elena de Bellard

Hereditary ataxia is a neurodegenerative disorder notable for its early onset, with symptoms appearing in patients as young as two years old. Although affected individuals exhibit severe motor deficits and early mortality rates, the timeline of Purkinje cell loss remains unclear. To address this gap, we used the spastic Han-Wistar rat model, which harbors an unknown homozygous recessive variant that causes Purkinje cell loss. Here, we determined the onset and temporal progression of Purkinje neuronal loss in the spastic Han-Wistar model. To achieve this, we employed immunohistochemistry, Hematoxylin and Eosin histology, and neuronal density quantification. Behavioral testing demonstrated early-onset, progressive motor impairment in mutant rats, with motor deficits emerging around P45, following Purkinje cell loss detectable as early as P15. Additionally, guided by pedigree analysis indicating autosomal recessive inheritance for this ataxia, we performed whole-genome shotgun sequencing of a parent-offspring trio to identify amino acid-changing mutations consistent with this pattern. Sanger sequencing excluded Sbf2 as a causal variant, and whole-genome sequencing identified 273 candidate genes consistent with autosomal recessive inheritance. Together, our findings provide new insights into the onset and genetic complexity of ataxia, refining the value of the spastic Han-Wistar rat as a model for investigating mechanisms underlying hereditary ataxia.

Introduction: Myelin is one of the most important features of the vertebrate nervous system, formed by glial cells. In the peripheral nervous system, Schwann cells produce myelin. While much is known about the molecules and processes involved in mammalian myelination, little is known about it in other vertebrate groups. Methods: In this study, we examined myelin development in the peripheral nerves of the turtle Trachemys scripta using qPCR, RNA sequencing, immunofluorescence, and TEM. Results: Our findings indicate that in T. scripta, myelination begins during the late stages of embryonic development and continues beyond hatching. Expression profiles reveal both conservation and divergence of core myelination components between mammals and amphibians; however, direct gene-level comparisons across species require further investigation given our small sample size Discussion: The upregulation of orthologous myelin genes in the turtle PNS supports the idea that these components are conserved, although their timing, regulation, or network structure may differ across tetrapods. We based our inference of conservation on orthology and the coordinated expression of key myelin genes (e.g., ErbB2, Mag, Mpz, Mbp, Pmp22) in T. scripta. TEM analysis of turtle sciatic nerves shows myelin rings in a few axons starting at stage 21, increasing significantly by stage 24, and becoming prominent in most axons of the adult nerve. Furthermore, antibodies against MPZ, DRP2, and Kv1.1 indicate that T. scripta adult peripheral nerves at various axial levels contain myelin segments with structures consistent with appositions and Schmidt-Lanterman incisures. Overall, this is the first study of PNS myelin development in a reptile, demonstrating that myelination is a highly conserved process in vertebrates.

Background: Turtles hold a unique place in vertebrate evolutionary history, making them critical assets in embryology research. Yet, they remain understudied as potential model organisms in the field. Here, to support experimental manipulations with turtle embryos, we have created a complete normal table of development for comprehensive embryonic staging of Trachemys scripta , one of the most common invasive turtle species worldwide. Results: The development of T. scripta embryos from 0 days post‐oviposition (DPO) to hatching (~60 DPO) was described from approximately 300 viable eggs collected at California State University, Northridge during the 2021–2024 nesting seasons. Thirty‐one stages between oviposition and hatching were identified, and anatomical structures were cataloged using the Standard Event System (SES) chart. Morphological characteristics were imaged using bright‐field microscopy and, for 4′,6‐diamidino‐2‐phenylindole‐stained embryos, confocal microscopy. Conclusion: To facilitate further research with Chelonian embryos, this staging series blends previously accepted staging practices with new details of T. scripta gastrulation, SES criteria, and a photographic annotated glossary.

Hereditary ataxia is a neurodegenerative disorder notable for its early onset, with symptoms appearing in patients as young as two years old. Although affected individuals exhibit severe motor deficits and early mortality rates, the timeline of Purkinje cell loss remains unclear. To address this gap, we used the spastic Han-Wistar rat model, which harbors an unknown homozygous recessive variant that causes Purkinje cell loss. Here, we aimed to determine the onset and temporal progression of Purkinje neuronal loss in the spastic Han-Wistar model. To achieve this, we employed immunohistochemistry, Hematoxylin and Eosin histology, and neuronal density quantification. Behavioral testing demonstrated early-onset, progressive motor impairment in mutant rats, which coincided with a gradual loss of Purkinje cells in the cerebellum. Additionally, guided by pedigree analysis from a previous study indicating autosomal recessive inheritance for this ataxia, we performed whole-genome shotgun sequencing of a parent-offspring trio to identify amino acid-changing mutations consistent with this pattern. We used Sanger sequencing to exclude non-causal candidates. Together, our findings provide new insights into the onset and genetic complexity of ataxia, refining the value of the spastic Han-Wistar rat as a model for investigating mechanisms underlying hereditary ataxia and broader neurodegenerative disorders.

The skin is the most extensive organ in vertebrates, composed of two layers: the epidermis and the dermis. Sensory axons originating from the dorsal root ganglia innervate the skin mechanoreceptors in the dermis. Elasmobranchs, which appeared 380 million years ago, are characterized by rough skin composed of dermal denticles. While we know about the epidermis and dermis of elasmobranchs, we do not know much about the presence or abundance of mechanoreceptors in their skin. Using the classic histological hematoxylin and eosin method, we examined the skins of hatchling embryos and adults Batoidea (skates and rays) and Selachimorpha (modern sharks). Our histology findings provide substantial evidence to identify structures with similar morphology to traditional mammalian and reptilian mechanoreceptors like Pacinian and Meissner corpuscles. An interesting observation was the presence of Pacinian in the skin of Batoidea but not in the skin of a Selachimorpha Squalus shark.

Hematoxylin and eosin stain is probably the most used staining method in histology. It provides a comprehensive and detailed picture of different types of cells and tissues. Preparing hard dermal tissues for H&E requires special steps. In this protocol, we describe what we found to work best for staining Elasmobranch skin and aim.

Chemokines are small signaling proteins released by cells in response to chemical stimuli in their environment. The chemokine stromal cell-derived factor-1 (SDF1/CXCL12) plays a role in the growth and metastasis of multiple cancers, including melanoma. SDF1/CXCL12 has two known receptors: CXCR4 and CXCR7. CXCR4 receptor signaling influences many cell responses, including the migration of neural crest cells and the amount of receptor expression upregulation in melanoma. CXCR7 receptor signaling influences melanocyte migration and constrains melanoma tumor growth in vivo, while CXCR4 receptor signaling does not. It is not known, however, if CXCR7 directly affects melanocyte and melanoma cell migration. Here, CXCR4 and CXCR7 receptor signaling were directly studied in vitro in human primary melanocytes and mouse B16-F10 melanoma cell line for migration when both receptors, individually and in combination, were genetically silenced. The silencing of CXCR7 clearly resulted in statistically significant inhibition of migration of both melanocytes and B16-F10 melanoma cells while the effects of CXCR4 silencing of migration inhibition was less clear. These results suggest that the CXCR7 receptor is more relevant than the CXCR4 receptor for the migratory capabilities of melanocytes and B16-F10 melanoma cells. These findings support down regulation or inhibition of the CXCR7 receptor through targeted therapies may be beneficial in melanoma treatment.

The Indo-Pacific is recognized as a hotspot for marine diversity. The taxonomy of certain taxa, such as Discomedusae jellyfish, has been neglected, despite its importance in the fishery industry. This study documents the first records of Discomedusae for the Java Sea using an integrative approach and provide notes about its distribution in the area. We used up to 53 morphological and meristic characters and amplified one mitochondrial marker (COI). The comparison and assessment of these data resulted in the recognition of seven species of Discomedusae, from which five has been recorded for the Indo-Pacific area. Two other species require a taxonomic revision to confirm the species assignation. The distribution of jellyfish in the coast of Java Sea might be correlated with the jellyfish life history and species-specific ranges of tolerance, and not solely determined by the environmental parameters. These findings provide the foundations for extending the taxonomic research in the area; the description of the biodiversity will increase the understanding of the population dynamics and its implications in the fisheries.

Background: Trunk neural crest cells (TNCC) are representing a model for epithelial to mesenchymal transition, this correlates the importance of studying the migration of these cells to cancer metastasis. Reptiles are unique group of animals being very morphologically diverse and their close position to synapsid leading to mammals. Recently, more publications focused on the migratory behavior of trunk NCC during embryonic development of squamates. Only one colubrid snake has been studied so far regarding the NCC migration. Results: Here we follow the migratory behavior of TNCC with HNK1 in the elapid snake Naja h. haje from early stage to 14 days postoviposition. Comparing the colubrid snake with the Egyptian cobra showed that both snakes overall follow the same TNCC migratory pathways of both birds and mammals by following the rostral and avoiding the caudal portions of the somites. Conclusions: First, TNCC intra-somitic migration as observed in turtles supports a contributing role for TNCC to scale precursors. Second, our observation of significant numbers of migrating TNCC in the intersomitic pathway suggest interesting evolutionary differences. Together, our present results of the Egyptian cobra in combination with those on a colubrid and turtle supports intersomitic TNCC as a unique reptile phenomena.