Biology subjects

Mikdache, A.

Publications and source records attributed to Mikdache, A..

6 recordsLinked to original sources

bioRxiv2025

Sox2 Regulates Lateral Line Morphogenesis via Yap/Taz-MediatedMechanotransduction

Organ morphogenesis relies on a tightly regulated interplay between cell proliferation, migration, and differentiation. Emerging evidence suggests that mechanical forces act alongside molecular signals to orchestrate tissue patterning, yet how these diverse inputs are integrated remains poorly understood. The zebrafish posterior lateral line offers a powerful in vivo model for studying how cellular behaviors and mechanosensitive signaling are spatiotemporally coordinated during organogenesis. Here, we identify the transcription factor Sox2 as a key regulator of lateral line morphogenesis, influencing the positioning, size, and number of neuromasts, the sensory organs of the lateral line. Loss of Sox2 leads to increased lateral line primordium cell proliferation, disrupted ZO1 deposition at the rosettes and smaller neuromasts positioned more posteriorly along the body axis, while Sox2 overexpression produces opposite phenotypes. Sox2 functions in part by repressing Yap/Taz(Wwtr1) signaling in the primordium. Reduced Yap/Taz activity results in more anterior neuromast deposition and premature termination of primordium migration. Furthermore, we show that as the primordium expands through cell-proliferation, increased cell-junction tension activates Yap/Taz, thereby influencing lateral line development. Reducing overproliferation in sox2-/-embryos diminishes the elevated Yap/Taz activity, supporting a model in which Sox2 limits proliferation to suppress Yap/Taz signaling and ensure proper primordium morphogenesis. These findings show that Sox2, together with the related SoxB1 transcription factor Sox3, regulates lateral line morphogenesis by coordinating primordium proliferation, neuromast size, and Yap/Taz-dependent mechanosensitive signaling.

developmental biology↗

bioRxiv2025

Interleukin-22 in enteroendocrine cells controls early-life gut motility through interactions with the microbiota

The gut microbiota, immune system, and enteric nervous system tightly interact to regulate adult gut physiology. Yet the mechanisms establishing gut physiology during development remain unknown. Here, we report that in developing zebrafish, enteroendocrine cells produce IL-22 in response to microbial signals before lymphocytes populate the gut. In larvae, IL-22 is crucial to set gut microbiota composition, and ghrelin hormone expression to promote gut motility. IL-22 developmental function depends on its ability to modulate gut microbiota, as bacterial transfer from wild-type zebrafish restored gut motility in il22-/- by reestablishing ghrelin hormone expression. Additionally, IL-22-deficient mice show impaired gut motility and reduced ghrelin expression in early life, indicating a conserved function. Altogether, we identify a circuit where enteroendocrine cells regulate gut function via cytokine control of the microbiota, showing how gut physiology is set prior to immune system maturation.

immunology↗

bioRxiv2024

Schwann cells have a limited window of time in which to initiate myelination program during early migration in vivo

The temporal control of mitotic exit of individual Schwann cells (SCs) is essential for radial sorting and peripheral myelination. However, it remains unknown when, during their multiple rounds of division, SCs initiate myelin signaling in vivo. By manipulating SC division during development, we report that when SCs skip their division during migration, but not during radial sorting, they fail to myelinate peripheral axons. This coincides with a sharp decrease in Laminin expression within the posterior lateral line nerve. Interestingly, elevating cAMP levels or forcing Laminin 2 expression within individual SCs restore their ability to myelinate, despite missing mitosis during migration. Our results demonstrate a limited time window during which migrating SCs initiate Laminin expression to activate the Laminin/Gpr126/cAMP signaling required for radial sorting and myelination at later stages in vivo.

developmental biology↗

bioRxiv2023

A non-invasive photoactivatable split-Cre recombinase system for genome engineering in zebrafish.

The cyclic recombinase (Cre)/loxP recombination system is a powerful technique for in vivo cell labeling and tracking. However, achieving high spatiotemporal precision in cell tracking using this system is challenging due to the requirement for reliable tissue-specific promoters. In contrast, light-inducible systems offer superior regional confinement, tunability and non-invasiveness compared to conventional lineage tracing methods. Here, we took advantage of the unique strengths of the zebrafish to develop an easy-to-use highly efficient, genetically encoded, Magnets-based, light-inducible transgenic Cre/loxP system. Our system relies on the reassembly of split Cre fragments driven by the affinity of the Magnets and is controlled by the zebrafish ubiquitin promoter. We demonstrate that our system does not exhibit phototoxicity or leakiness in the dark, and it enables efficient and robust Cre/loxP recombination in various tissues and cell types at different developmental stages through noninvasive illumination with blue light. Our newly developed tool is expected to open novel opportunities for light-controlled tracking of cell fate and migration in vivo. HighlightsO_LIzPA-Cre is a novel zebrafish transgenic optogenetic split-Cre tool C_LIO_LIzPA-Cre allows loxP-mediated DNA recombination in various tissues and cell types C_LIO_LIIt enables light-induced DNA recombination at different developmental stages. C_LIO_LIIt allows spatio-temporal DNA recombination in a specific tissue region with high resolution C_LI

developmental biology↗

bioRxiv2023

A layered erythromyeloid ontogeny ensures timely supply of erythrocytes and macrophages during development

In all organisms studied, from flies to humans, blood cells emerge in several sequential waves and from distinct hematopoietic origins. However, the relative contribution of these ontogenetically distinct hematopoietic waves to embryonic blood lineages and to tissue regeneration during development is yet elusive. Here, using a lineage-specific switch and trace strategy in the zebrafish embryo, we report that the definitive hematopoietic progeny barely contributes to erythrocytes and macrophages during early development. Lineage tracing further show that ontogenetically distinct macrophages exhibit differential recruitment to the site of injury based on the developmental stage of the organism. We further demonstrate that primitive macrophages can solely maintain tissue regeneration during early larval developmental stages after selective ablation of definitive macrophages. Our findings highlight that the sequential emergence of hematopoietic waves in embryos ensures the abundance of blood cells required for tissue homeostasis and integrity during development. O_FIG O_LINKSMALLFIG WIDTH=145 HEIGHT=200 SRC="FIGDIR/small/529211v2_ufig1.gif" ALT="Figure 1"> View larger version (33K): org.highwire.dtl.DTLVardef@c4cd30org.highwire.dtl.DTLVardef@7b38deorg.highwire.dtl.DTLVardef@1d28ea9org.highwire.dtl.DTLVardef@940784_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

bioRxiv2022

Timely Schwann cell division during migration drives peripheral myelination in vivo via Laminin/cAMP pathway

Schwann cells (SC) migrate along peripheral axons and divide intensively to generate the right number of cells prior to axonal ensheathment; however, little is known regarding the temporal and molecular control of their division, particularly during migration, and its impact on myelination. We report that Sil, a spindle pole protein associated with autosomal recessive primary microcephaly (MCPH), is required for temporal mitotic exit of SC. In sil-deficient cassiopeia (csp-/-) mutants, SC fail to radially sort and myelinate peripheral axons. Elevation of cAMP, but not Rac1 activity in csp-/- restores myelin ensheathment. Most importantly, we show a significant decrease in Laminin expression within csp-/- posterior lateral line nerve and that forcing Laminin2 expression in csp-/- fully restores SC ability to myelinate. We also discovered that SC have a restricted time window during which they have to divide, while migrating, in order to trigger myelination. Thus, we unravel a novel and essential role for timely SC division during migration in mediating Laminin expression to orchestrate radial sorting and peripheral myelination in vivo.

developmental biology↗