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Mikdache, A.

Publications and source records attributed to Mikdache, A..

2 recordsLinked to original sources

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↗

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↗