Perinatal liver sympathetic innervation governs body size

Authors
Bobo-Jimenez, Veronica, Gomila, Silvia, Lapresa, Rebeca, Agulla, Jesus, Angibaud, Julie, Sanchez-Moran, Irene, Delgado-Esteban, Maria, González-Rodriguez, Agueda, Fernández-Jaén, Alberto, Ramos-Cabrer, Pedro, Nägerl, U. Valentin, Bolaños, Juan P., Almeida, Angeles


Lab
Bilbao

Journal
Communications Biology

Abstract
Perinatal failure in the growth hormone (GH)-insulin-like growth factor-1 (IGF-1) axis causes impaired body growth and central and autonomous neurodevelopmental disorders. However, whether a primary neurodevelopmental disorder causes organ misinnervation as a contributing factor in growth retardation is elusive. To interrogate this, here we generated a late embryonic neural-specific cdc20 homolog 1 (Cdh1) knockout mouse model, which exhibited a primary delay in early postnatal brain development. These mice displayed an intact GH-releasing hormone (GHRH)-GH-hepatic GH receptor (GHR) pathway despite a body growth retardation that could be reversed by IGF-1 administration in the early postnatal life. Mechanistically, liver sympathetic misinnervation impaired signal transducers and activators of transcription 5 (STAT5) phosphorylation, required for liver IGF-1 biosynthesis and release. We also report decreased blood levels of IGF-1 in a patient harboring a pathogenic mutation in Cdh1 that causes neurodevelopmental and growth delay. Taken together, these findings demonstrate that a primary neurodevelopmental defect disrupts sympathetic hepatic innervation, leading to a GH-independent growth retardation, thus establishing a positive feedback loop that propagates the disease presentation. A primary neurodevelopmental disorder controls liver IGF-1 secretion to boost organismal growth through a GH pathway-independent. Hepatic sympathetic misinnervation causes liver steatosis and fibrosis, leading to impaired GHR-JAK2-STAT5 pathway and IGF1 biosynthesis.

Keywords/Topics
Developmental disorders; Molecular neuroscience

BIOSEB Instruments Used:
Grip strength test (BIO-GS4)

Source :

https://www.nature.com/articles/s42003-026-09880-9

Related products

Grip strength test

Publication request

Thank you for your interest in our product range and your request for this publication, which will be sent to you if the research team and the journal allow it. Our commercial team will contact you as soon as possible.