# Genetic requirement for Esrp1 and Esrp2 in vertebrate pituitary morphogenesis

## TL;DR

This study shows that Esrp1 and Esrp2 are essential for pituitary development and are linked to cleft palate and hypopituitarism.

## Contribution

The study identifies a novel genetic requirement for Esrp1/2 in pituitary morphogenesis and links ESRP2 variants to human craniofacial and pituitary defects.

## Key findings

- Esrp1/2 are required for pituitary development in mice and zebrafish.
- A human case with cleft palate and hypopituitarism has a variant in ESRP2's RNA-binding domain.
- Esrp1/2 play a key role in both orofacial and pituitary development.

## Abstract

The pituitary gland produces several hormones that regulate growth, metabolism, stress response, reproduction and homeostasis. Congenital hypopituitarism is a deficiency in one or more pituitary hormones and encompasses a spectrum of clinical conditions. The pituitary has a complex embryonic origin, with the oral ectoderm contributing the anterior lobe, and the neural ectoderm generating the posterior lobe. Pituitary abnormalities and growth deficiencies are associated with cleft palate; however, the developmental genetic connection between pituitary and orofacial cleft malformations remains to be determined. The epithelial RNA splicing regulators Esrp1 and Esrp2 (Esrp1/2) are required for orofacial development in zebrafish, mice and humans, and loss of function of these genes results in a cleft palate. Here, we present a detailed developmental analysis of the genetic requirement for Esrp1/2 in pituitary morphogenesis in mouse and zebrafish. Further, we describe an individual with cleft palate and hypopituitarism who harbors a nucleotide variant in the RNA-binding domain of ESRP2. The discovery of this key function for Esrp1/2 in pituitary formation has significant fundamental and clinical implications for understanding congenital hypopituitarism and craniofacial anomalies.

Summary: The role of Esrp1 and Esrp2 in orofacial and pituitary development has significant fundamental and clinical implications for understanding congenital hypopituitarism and craniofacial anomalies.