Biology subjects

Belahbib, H.

Publications and source records attributed to Belahbib, H..

3 recordsLinked to original sources

bioRxiv2023

MAFB drives differentiation by permitting WT1 binding to podocyte 1 specific promoters

Podocytes are highly specialized cells, but their chromatin status and the precise molecular events leading to their differentiation remain poorly defined. Here we used ChIP-Seq analysis for H3K4me3, H3K4me1 and H3K27me3 to establish the histone methylation map in adult mouse podocytes. Our data demonstrate open chromatin across podocyte specific genes and reveals that genes expressed in the mesoderm lineage become actively repressed upon podocyte differentiation. To better understand the transcriptional control of podocyte differentiation, we studied the role of transcription factor MAFB. ChIP-Seq experiments and functional analysis in conditional knockout mice identified a set of direct MAFB targets including Nphs1, Nphs2, Vegfa and Tcf21. Loss of MafB led to the deposition of extracellular matrix, progressive foot process effacement, and kidney disease. ChIP experiments in knockout animals revealed that during development MAFB is essential for H3K4me3 methylation and the recruitment of WT1 to the promoters of the podocyte specific genes Nphs1 and Nphs2. Taken together our data reveal the crucial function of MAFB by permitting chromatin accessibility at podocyte-specific genes during development and maintaining terminal differentiation in adults.

developmental biology↗

bioRxiv2022

The compact genome of the sponge Oopsacas minuta (Hexactinellida) is lacking key metazoan core genes

BackgroundBilaterian animals today represent 99% of animal biodiversity. Elucidating how bilaterian hallmarks emerged is a central question of animal evo-devo and evolutionary genomics. Studies of non-bilaterian genomes have suggested that the ancestral animal already possessed a diversified developmental toolkit, including some pathways required for bilaterian body plans. Comparing genomes within the early branching metazoan Porifera phylum is key to identify which changes and innovations contributed to the successful transition towards bilaterians. ResultsHere, we report the first whole genome comprehensive analysis of a glass sponge, Oopsacas minuta, a member of the Hexactinellida. Studying this class of sponge is evolutionary relevant because it differs from the three other Porifera classes in terms of development, tissue organization, ecology and physiology. Although O. minuta does not exhibit drastic body simplifications, its genome is among the smallest animal genomes sequenced so far, surprisingly lacking several metazoan core genes (including Wnt and several key transcription factors). Our study also provided the complete genome of the symbiotic organism dominating the associated microbial community: a new Thaumarchaeota species. ConclusionsThe genome of the glass sponge O. minuta differs from all other available sponge genomes by its compactness and smaller number of predicted proteins. The unexpected losses of numerous genes considered as ancestral and pivotal for metazoan morphogenetic processes most likely reflect the peculiar syncytial organization in this group. Our work further documents the importance of convergence during animal evolution, with multiple emergences of sponge skeleton, electrical signaling and multiciliated cells.

evolutionary biology↗

bioRxiv2017

NEW GENOMIC DATA AND ANALYSES CHALLENGE THE TRADITIONAL VISION OF ANIMAL EPITHELIUM EVOLUTION

The emergence of epithelia was the foundation of metazoan expansion. To investigate the early evolution of animal epithelia, we sequenced the genome and transcriptomes of two new sponge species to characterize epithelial markers such as the E-cadherin complex and the polarity complexes for all classes (Calcarea, Demospongiae, Hexactinellida, Homoscleromorpha) of sponges (phylum Porifera) and compare them with their homologs in Placozoa and in Ctenophora. We found that Placozoa and most sponges possess orthologs of all essential genes encoding proteins characteristic of bilaterian epithelial cells, as well as their conserved interaction domains. In stark contrast, we found that ctenophores lack several major polarity complex components such as the Crumbs complex and Scribble. Furthermore, the E-cadherin ctenophore ortholog exhibits a divergent cytoplasmic domain making it unlikely to interact with its canonical cytoplasmic partners. These unexpected findings challenge the current evolutionary paradigm on the emergence of epithelia.\n\nSIGNIFICANT STATEMENTEpithelial tissues are a hallmark of metazoans deeply linked to the evolution of the complex morphogenesis processes characterizing their development. However, studies on the epithelial features of non-bilaterians are still sparse and it remains unclear whether the last common metazoan ancestor possessed a fully functional epithelial toolkit or if it was acquired later during metazoan evolution. In this work, we demonstrate that if sponges have a well conserved and functionally predicted epithelial toolkit, Ctenophores have either divergent adhesion complexes or lack essential polarity complexes. Altogether, our results raise a doubt on the homology of protein complexes and structures involved in cell polarity and adhesive type junctions between Ctenophora and Bilateria epithelia.

evolutionary biology↗