Biology subjects

Gjorcheska, S.

Publications and source records attributed to Gjorcheska, S..

3 recordsLinked to original sources

bioRxiv2024

Midfacial retrusion and loss of facial appendages caused by mutation of Pax9 in zebrafish

Loss of dentition has occurred repeatedly throughout vertebrate evolution. Cyprinid fish, including zebrafish, form teeth only deep within the pharynx, not on their oral jaws. However, zebrafish still robustly express transcription factors associated with mammalian tooth development in the neural crest-derived mesenchyme surrounding the mouth. We investigated whether this expression is vestigial or whether these factors contribute to the formation of non-tooth mesenchymal structures in the oral region, using Pax9 as a test case. Zebrafish homozygous for two different pax9 mutant alleles develop the normal complement of pharyngeal teeth but fail to form the premaxilla bone, most of the maxilla, and nasal and maxillary barbels. Lack of most of the upper jaw complex does not preclude effective feeding in the laboratory environment. We observed a significant deficit of sp7:EGFP+ osteoblasts and adjacent alx4a:DsRed+ condensing mesenchyme where the maxilla forms, and no accumulation of either in the premaxillary domain. These phenotypes are not presaged by major disruptions in early facial patterning, Wnt signaling, proliferation, or cell death; however, loss of a small population of Wnt-responsive cells around the maxilla correlates with its stalled growth in mutants. We conclude that Pax9 is not unequivocally required for all vertebrate tooth development, but instead may be broadly involved in the development of a variety of organs forming through mesenchymal condensation around the mouth.

developmental biology↗

bioRxiv2024

Cadherin 16 promotes sensory gating via the endocrine corpuscles of Stannius

Sensory thresholds enable animals to regulate their behavioral responses to environmental threats. Despite the importance of sensory thresholds for animal behavior and human health, we do not yet have a full appreciation of the underlying molecular-genetic and circuit mechanisms. The larval zebrafish acoustic startle response provides a powerful system to identify molecular mechanisms underlying establishment of sensory thresholds and plasticity of thresholds through mechanisms like habituation. Using this system, we identify Cadherin 16 as a previously undescribed regulator of sensory gating. We demonstrate that Cadherin 16 regulates sensory thresholds via an endocrine organ, the corpuscle of Stannius (CS), which is essential in zebrafish for regulating Ca2+ homeostasis. We further show that Cadherin 16 regulates whole-body calcium and ultimately behavior through the hormone Stanniocalcin 1L, and the IGF-regulatory metalloprotease, Papp-aa. Finally, we demonstrate the importance of the CS through ablation experiments that reveal its role in promoting normal acoustic sensory gating. Together, our results uncover a previously undescribed brain non-autonomous pathway for the regulation of behavior and establish Ca2+ homeostasis as a critical process underlying sensory gating in vivo.

genetics↗

bioRxiv2024

Sox10 is required for systemic initiation of bone mineralization

Heterozygous variants in the gene encoding the SOX10 transcription factor cause congenital syndromes affecting pigmentation, digestion, hearing, and neural function. Most of these symptoms are attributable to failed differentiation and loss of neural crest cells. Extensive research on mouse and zebrafish models has confirmed that Sox10 is essential for most non-skeletal crest derivatives, but seemingly dispensable for skeletal development. We challenge that concept here by revealing a novel requirement for Sox10 in skeletal mineralization. Neither neural crest- nor mesoderm-derived bones initiate mineralization on time in zebrafish sox10 mutants, despite normal osteoblast differentiation and matrix production. We show that mutants are deficient in the ionocyte subpopulation tasked with taking up calcium from the environment through the Trpv6 epithelial calcium channel, leading to a severe calcium deficit that explains the lack of mineralization. As these ionocytes do not derive from a sox10+ lineage, we hypothesized that the primary defect instead resides in a separate organ that regulates ionocyte numbers or calcium uptake at a systemic level. Screening of the endocrine hormones known to regulate calcium homeostasis in adult vertebrates revealed significantly elevated levels of stanniocalcin (Stc1a), an anti-hypercalcemic hormone, in larval sox10 mutants. Previous studies demonstrated that Stc1a inhibits calcium uptake in fish by repressing trpv6 expression and blocking proliferation of Trpv6+ ionocytes. Our epistasis assays indicate that excess Stc1a is the proximate cause of the calcium deficit in sox10 mutants. Lineage tracing shows that the pronephros-derived glands that synthesize Stc1a interact with sox10+ neural crest-derived cells, and that the latter are missing in mutants. We conclude that a subpopulation of Sox10+ neural crest non-cell-autonomously limit Stc1a production to allow the inaugural wave of calcium uptake necessary for the initiation of bone mineralization.

developmental biology↗