E2f4 is required for intestinal and otolith development in zebrafish

Abstract

E2f4 is a multifunctional transcription factor that is essential for many cellular processes. Although the role of E2f4 during cell cycle progression has been investigated in great detail, less is known about E2f4 during embryonic development.Here, we investigated the role of E2f4 during zebrafish development. Zebrafish e2f4 mutants displayed ectopic otolith formation due to abnormal ciliary beating in the otic vesicle. The beating defects of motile cilia were caused by abnormal expression of ciliary motility genes. The expression of two genes, lrrc23 and ccdc151, were significantly decreased in the absence of E2f4. In addition to that, e2f4 mutants also displayed growth retardation both in the body length and body weight and mostly died at around 6 months old. Although food intake was normal in the mutants, we found that the microvilli of the intestinal epithelia were significantly affected in the mutants. Finally, the intestinal epithelia of e2f4 mutants also displayed reduced cell proliferation, together with an increased level of cell apoptosis. Our data suggested a tissue-specific role of E2f4 during zebrafish development, which is distinct from the traditional views of this protein as a transcription repressor.

The role of cilia during organogenesis in zebrafish

“…Moreover, the pattern of ciliary beating in zebrafish is also diverse. Motile cilia in the KV and early otic placode exhibit a circular beating pattern [ 80 ]. In the pronephric/kidney duct, motile cilia show a rhythmic sinusoidal wave pattern, while in the central canal and ventricles, the beating pattern is back and forth [ 42 , 73 ].…”

Special issue: Cilia and ciliopathies

“…Being a specialized cellular antenna, cilia are essential for the transduction of variety of signals, including Hedgehog signaling. The review from Jin et al (2022) explore the roles of prostaglandin signaling during ciliogenesis and development. Prostaglandin E2 (PGE2) binds its receptor, EP4, on the ciliary membrane and activates downstream cAMP signals to promote ciliogenesis.…”

“…Prostaglandin E2 (PGE2) binds its receptor, EP4, on the ciliary membrane and activates downstream cAMP signals to promote ciliogenesis. Jin et al (2022) outline recent advances in prostaglandin signaling during ciliogenesis, embryonic development and organogenesis.…”

“…Removal of YAP1, specifically in the retinal Muller cells, causes extensive late‐onset retinal degeneration, including cone and rod photoreceptors that have the highly specialized connecting cilium. Jin et al (2022) studied the role of E2f4 during zebrafish intestine and otolith development. E2f4 regulates the expression of ciliary motility genes, thus, contributing to coordinated ciliary motility in the otic vesicles.…”