S-020 | LOSS OF INSULIN-LIKE GROWTH FACTOR 1 (IGF1) LEADS TO DEFECTS IN HAIR CELL FUNCTION IN DEVELOPING ZEBRAFISH EMBRYOS

Cellular and Molecular Neurobiology
Author: Macarena Lucia Recalcatti | Email: macarenaluciarecalcatti@gmail.com

Macarena Recalcatti^1°, Lucía Salatino^2°, María Celia Fernández^1°,  Ayelén Martin^1°, Horacio Domené^1°, Patricia Pennisi^1°, Paola Plazas^2°,  Sabina Domené^1°

^1° Centro de Investigaciones Endocrinológicas “Dr. César Bergadá” (CEDIE), CONICET–FEI–División de Endocrinología, Hospital de Niños Ricardo Gutiérrez, Buenos Aires C1425EFD, Argentina.
^2° Instituto de Farmacología, Facultad de Medicina, Universidad de Buenos Aires (UBA), Paraguay 2155, C1121ABG, Buenos Aires, Argentina.

The insulin-like growth factor 1 (IGF1) is highly conserved among vertebrates and plays a central role in pre and postnatal growth. IGF1 deficiency due to homozygous pathogenic variants in the IGF1 human gene leads to intrauterine and postnatal delay of growth sometimes associated with deafness and mental retardation.
To study the role of igf1 in hair cells development we generated a morpholino (MO)-mediated igf1 knockdown phenotype in zebrafish and evaluated the effects on ear and lateral line structure and function. Staining with the fluorophore 4-Di-2-Asp (DIASP) was performed on live MO-injected larvae at 5 days post-fertilization (dpf) to assess hair cells function.
Preliminary results showed that MO-mediated knockdown of igf1 led to a 28% decrease in neuromast fluorescence intensity in morphant embryos compared to MO control (p= 0.0003). Moreover, morphant embryos showed a reduction of total otolith area in the otic vesicle compared to MO control embryos (5720.5 versus 7003.9 µm3, p<0.0001). Finally, morphant embryos displayed cardiovascular abnormalities including pericardial edema and lower cardiac frequency compared to MO control embryos (120.8 versus 141.1 bpm, p< 0.0001). In conclusion, our study showed that igf1 contributes to the correct development of the otoliths and hair cells function in zebrafish embryos. This model will allow to study the underlying role of IGF1 in the development of deafness and mental retardation in human patients with IGF1 deficiency