RT Journal Article
T1 A selective defect in the glial wedge as part of the neuroepithelium disruption in hydrocephalus development in the mouse hyh model is associated with complete corpus callosum dysgenesis.
A1 Rodríguez-Pérez, Luis Manuel
A1 López-de-San-Sebastián, Javier
A1 De-Diego-Barbado, Isabel
A1 Smith-Fernández, José Aníbal
A1 Roales-Buján, Ruth
A1 Jiménez-Lara, Antonio Jesús
A1 Páez-González, Patricia
K1 Agenesia del cuerpo calloso
K1 Hidrocefalia - Modelos animales
AB INTRODUCTION Dysgenesis of the corpus callosum is present in neurodevelopmental disorders and coexists with hydrocephalus in several human congenital syndromes. The mechanisms that underlie the etiology of congenital hydrocephalus and agenesis of the corpus callosum when they coappear during neurodevelopment persist unclear. In this work, the mechanistic relationship between both disorders is investigated in the hyh mouse model for congenital hydrocephalus, which also develops agenesis of the corpus callosum. In this model, hydrocephalus is generated by a defective program in the development of neuroepithelium during its differentiation into radial glial cellsMETHODS In this work, the populations implicated in the development of the corpus callosum were studied in wild-type and hyh mutant mice. Immunohistochemistry, mRNA in situ hybridization, axonal tracing experiments, and organotypic cultures from normal and hyh mouse embryos were usedRESULTS Our results show that the defective program in the neuroepithelium/radial glial cell development in the hyh mutant mouse selectively affects the glial wedge cells. The glial wedge cells are required to guide the pioneering axons as they approach the corticoseptal boundary. The pioneering callosal axons arising from neurons in the cingulate cortex can extend projections to the interhemispheric midline in normal and hyh mice. However, pioneering axons in the hyh mutant mouse, when approaching the area corresponding to the damaged glial wedge cell population, turned towards the ipsilateral lateral ventricle. This defect occurred before ventriculomegaly appearanceDISCUSSION The abnormal development of the ventricular zone, apparently inherent to the etiology of several forms of congenital hydrocephalus, can explain, in some cases, the common association between hydrocephalus and corpus callosum dysgenesis. Further studies may be needed to understand the corpus callosum dysgenesis etiology when it concurs with hydrocephalus
PB Frontiers
YR 2024
FD 2024-02-21
LK https://hdl.handle.net/10630/37726
UL https://hdl.handle.net/10630/37726
LA eng
NO The author(s) declare financial support was received for the research, authorship, and/or publication of this article. The present work was supported by grants PI12/00631 (to AJ) and PI19/00778 (to AJ and PP-G) from the Instituto de Salud Carlos III, Spain, cofinanced by FEDER funds from the European Union; RYC-2014-16980 to PP-G from the Ministerio de Economía y Competitividad, Spain; UMA18-FEDERJA-277 from Plan Operativo FEDER Andalucía 2014–2020 and Universidad de Málaga to PP-G; Contrato Postdoctoral-PPITD-UMA from Universidad de Málaga to L-MR-P; and Proyectos Dirigidos por Jóvenes Investigadores from Universidad de Málaga to PP-G.
DS RIUMA. Repositorio Institucional de la Universidad de Málaga
RD 12 abr 2026