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This text analyses the first two decades of the École normale supérieure d’institutrices situated in Fontenay-aux-Roses since its foundation in 1880. Created to train elite female primary teaching staff (headmistresses and teachers in teacher training colleges, female inspectors of primary schools, etc.), the school of Fontenay was deeply influenced by its director of studies: Félix Pécaut (1828-1898). A supporter of an ambitious programme of instruction for women and an advocate of a model of laïcité (secularity) derived from his own belonging to the protestant religion, Félix Pécaut encouraged the “fontenaysiennes” to develop their critical thinking and apply it to every subject. This research analyses the youth of the Fontenay school through the mark that Pécaut made on a dozen of his students. This research is based on texts written by several of his former pupils who spoke up at the turn of the century when attacks against the school were proliferating in the context of the “War between the two Frances” (“Guerre des deux France”). Pécaut being a Dreyfus supporter, he converted Ferdinand Buisson to his cause and led his former pupils to keep a vigilant eye on the situation of the country in this context of political and social crisis. During this chaotic period, the school of Fontenay was frequently attacked in the press. Several “fontenaysiennes” stayed faithful to the legacy of Pécaut in their own teacher training colleges during the Belle Époque. They applied a liberal discipline based on self-government, replicating the traditional morning conferences and keeping in mind Pécaut’s aphorism addressed to “his daughters”: “Dare to be!”.‪, Cet article revient sur les deux premières décennies d’existence de l’École normale supérieure d’institutrices de Fontenay-aux-Roses à partir de sa fondation en 1880. Créée pour former l’élite du corps enseignant primaire féminin (les directrices et professeures d’écoles normales, d’écoles primaires supérieures et les inspectrices), l’école de Fontenay est marquée pendant cette période par l’aura de son directeur des études : Félix Pécaut (1828-1898). Défenseur d’une instruction ambitieuse pour les filles et partisan d’une conception de la laïcité scolaire maintenant une aspiration à la transcendance, cet ancien pasteur protestant encourage les fontenaysiennes à développer leur esprit critique et le principe du libre examen en tout domaine. C’est à travers l’empreinte que Pécaut a laissée sur une dizaine de fontenaysiennes que cet article aborde la jeunesse de l’école de Fontenay. Cette recherche repose sur les textes produits par plusieurs anciennes élèves de « Monsieur l’Inspecteur », qui s’expriment, pour beaucoup d’entre elles, au tournant du XIXᵉ et du XXᵉ siècle, alors que les attaques se multiplient contre Fontenay dans le contexte de la « Guerre des deux France ». L’engagement dreyfusard de Félix Pécaut, qui entraîne avec lui Ferdinand Buisson et qui appelle la communauté des fontenaysiennes à la vigilance, attire en effet sur l’école de Fontenay les foudres de l’opinion conservatrice. La fin du siècle est l’occasion de batailles de plumes dans la presse autour de l’École normale supérieure d’institutrices. De nombreuses fontenaysiennes font malgré tout fructifier l’héritage de Pécaut dans leurs écoles normales pendant toute la Belle Époque, appliquant une discipline libérale fondée sur le self-government, reprenant la tradition des conférences du matin et gardant en tête la maxime pécaldienne adressée à « ses filles » : « Osez être ! ».

International audience; Maturity-onset diabetes of the young type 5 (MODY5) is due to heterozygous mutations or deletion of HNF1B. No mouse models are currently available to recapitulate the human MODY5 disease. Here, we investigate the pancreatic phenotype of a unique MODY5 mouse model generated by heterozygous insertion of a human HNF1B splicing mutation at the intron-2 splice donor site in the mouse genome. This Hnf1bsp2/+ model generated with targeted mutation of Hnf1b mimicking the c.544+1G>T (T) mutation identified in humans, results in alternative transcripts and a 38% decrease of native Hnf1b transcript levels. As a clinical feature of MODY5 patients, the hypomorphic mouse model Hnf1bsp2/+ displays glucose intolerance. Whereas Hnf1bsp2/+ isolated islets showed no altered insulin secretion, we found a 65% decrease in pancreatic insulin content associated with a 30% decrease in total large islet volume and a 20% decrease in total β-cell volume. These defects were associated with a 30% decrease in expression of the pro-endocrine gene Neurog3 that we previously identified as a direct target of Hnf1b, showing a developmental etiology. As another clinical feature of MODY5 patients, the Hnf1bsp2/+ pancreases display exocrine dysfunction with hypoplasia. We observed chronic pancreatitis with loss of acinar cells, acinar-to-ductal metaplasia, and lipomatosis, with upregulation of signaling pathways and impaired acinar cell regeneration. This was associated with ductal cell deficiency characterized by shortened primary cilia. Importantly, the Hnf1bsp2/+ mouse model reproduces the pancreatic features of the human MODY5/HNF1B disease, providing a unique in vivo tool for molecular studies of the endocrine and exocrine defects and to advance basic and translational research. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.

International audience; The transcription factors HNF1B and Pax2, co-expressed in the Wolffian duct and ureteric bud epithelia, play essential roles during the early steps of mouse kidney development. In humans, heterozygous mutations in these genes display a number of common kidney phenotypes, including hypoplasia and multicystic hypoplastic kidneys. Moreover, a high prevalence of mutations either in HNF1B or PAX2 has been observed in children with renal hypodysplasia. To gain a better understanding of Hnf1b and Pax2 interactions in vivo, we generated compound heterozygous mice for Hnf1b and Pax2 null alleles. We show here that compound heterozygous mutants display phenotypes similar to severe congenital anomalies of the kidney and the urinary tract (CAKUT), including strong hypoplasia of the kidneys, caudal ectopic aborted ureter buds, duplex kidneys, megaureters and hydronephrosis. At a molecular level, compound mutants show a delay in nephron segment and medullar interstitial differentiation, increased apoptosis and a transient decrease in Lim1 and Wnt4 expression. We also observe a perturbation of smooth muscle differentiation around the ureter associated with a local down-regulation in transcript levels of Bmp4 and Tbx18, two key regulators involved in ureter smooth muscle formation, thus explaining, at least in part, megaureters. These results together uncover a novel role of Hnf1b as a modifier of the Pax2 haplo-insufficient phenotype and show that these two transcription factors operate in common pathways governing both kidney morphogenesis and ureter differentiation. This mouse model should provide new insights into the pathogenic mechanisms of human CAKUT, the most frequent developmental defect identified in newborns.