Biology subjects

Camargo Sosa, K.

Publications and source records attributed to Camargo Sosa, K..

4 recordsLinked to original sources

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↗

bioRxiv2021

Zebrafish pigment cells develop directly from persistent highly multipotent progenitors.

Neural crest cells (NCCs) are highly multipotent stem cells. A long-standing controversy exists over the mechanism of NCC fate specification, specifically regarding the presence and potency of intermediate progenitors. The direct fate restriction (DFR) model, based on early in vivo clonal studies, hypothesised that intermediates are absent and that migrating cells maintain full multipotency1-6. However, most authors favour progressive fate restriction (PFR) models, with fully multipotent early NCCs (ENCCs) transitioning to partially-restricted intermediates before committing to individual fates7-12. Here, single cell transcriptional profiling of zebrafish pigment cell development leads to us proposing a Cyclical Fate Restriction mechanism of NCC development that reconciles the DFR and PFR models. Our clustering of single NCC Nanostring transcriptional profiles identifies only broadly multipotent intermediate states between ENCCs and differentiated melanocytes and iridophores. Leukocyte tyrosine kinase (Ltk) marks the multipotent progenitor and iridophores, consistent with biphasic ltk expression13-15. Ltk inhibitor and constitutive activation studies support expression at an early multipotent stage, whilst lineage-tracing of ltk-expressing cells reveals their multipotency extends beyond pigment cell-types to neural fates. We conclude that pigment cell development does not involve a conventional PFR mechanism, but instead occurs directly and more dynamically from a broadly multipotent intermediate state.

developmental biology↗

bioRxiv2021

Novel Generic Models for Differentiating Stem Cells Reveal Oscillatory Mechanisms

Understanding cell fate selection remains a central challenge in developmental biology. We present a class of simple yet biologically-motivated mathematical models for cell differentiation that generically generate oscillations and hence suggest alternatives to the standard framework based on Waddingtons epigenetic landscape. The models allow us to suggest two generic dynamical scenarios that describe the differentiation process. In the first scenario gradual variation of a single control parameter is responsible for both entering and exiting the oscillatory regime. In the second scenario two control parameters vary: one responsible for entering, and the other for exiting the oscillatory regime. We analyse the standard repressilator and four variants of it and show the dynamical behaviours associated with each scenario. We present a thorough analysis of the associated bifurcations and argue that gene regulatory networks with these repressilator-like characteristics are promising candidates to describe cell fate selection through an oscillatory process.

developmental biology↗

bioRxiv2018

Endothelin receptor Aa regulates proliferation and differentiation of Erb-dependant pigment progenitors in zebrafish

Skin pigment patterns are important, being under strong selection for multiple roles including camouflage and UV protection. Pigment cells underlying these patterns form from adult pigment stem cells (APSCs). In zebrafish, APSCs derive from embryonic neural crest cells, but sit dormant until activated to produce pigment cells during metamorphosis. The APSCs are set-aside in an ErbB signaling dependent manner, but the mechanism maintaining quiescence until metamorphosis remains unknown. Mutants for a pigment pattern gene, parade, exhibit ectopic pigment cells localised to the ventral trunk. We show that parade encodes Endothelin receptor Aa, expressed in the blood vessels. Using chemical genetics, coupled with analysis of cell fate studies, we show that the ectopic pigment cells derive from APSCs. We propose that a novel population of APSCs exists in association with medial blood vessels, and that their quiescence is dependent upon Endothelin-dependent factors expressed by the blood vessels.\n\nLay AbstractPigment patterns are crucial for the many aspects of animal biology, for example, providing camouflage, enabling mate selection and protecting against UV irradiation. These patterns are generated by one or more pigment cell-types, localised in the skin, but derived from specialised stem cells (adult pigment stem cells, APSCs). In mammals, such as humans, but also in birds and fish, these APSCs derive from a transient population of multipotent progenitor cells, the neural crest. Formation of the adult pigment pattern is perhaps best studied in the zebrafish, where the adult pigment pattern is formed during a metamorphosis beginning around 21 days of development. The APSCs are set-aside in the embryo around 1 day of development, but then remain inactive until that metamorphosis, when they become activated to produce the adult pigment cells. We know something of how the cells are set-aside, but what signals maintain them in an inactive state is a mystery. Here we study a zebrafish mutant, called parade, which shows ectopic pigment cells in the embryo. We clone the parade gene, identifying it as ednraa encoding a component of a cell-cell communication process, which is expressed in blood vessels. By characterising the changes in the neural crest and in the pigment cells formed, and by combining this with an innovative assay identifying drugs that prevent the ectopic cells from forming, we deduce that the ectopic cells in the larva derive from precocious activation of APSCs to form pigment cells. We propose that a novel population of APSCs are associated with the blood vessels, that these are held in a quiescent state by signals coming from these vessels, and that these signals depend upon ednraa. Together this opens up an exciting opportunity to identify the signals maintaining APSC quiescence in zebrafish.

developmental biology↗