Distinct requirements of E2f4 versus E2f5 activity for multiciliated cell development in the zebrafish embryo

• Published in: Developmental biology Vol. 443; no. 2; pp. 165 - 172
• Main Authors: Chong, Yan Ling, Zhang, Yiliu, Zhou, Feng, Roy, Sudipto
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.11.2018
• Subjects: Animals; Cell Cycle Proteins - metabolism; Cell Differentiation - genetics; Cilia; Cilia - metabolism; Cilia - physiology; E2f4; E2F4 Transcription Factor - metabolism; E2F4 Transcription Factor - physiology; E2f5; E2F5 Transcription Factor - metabolism; E2F5 Transcription Factor - physiology; Gene Expression Regulation, Developmental - genetics; Gmnc; HEK293 Cells; Humans; Multiciliated cell; Multicilin; Nuclear Proteins - metabolism; Transcription Factors; Zebrafish; Zebrafish - embryology; Zebrafish - genetics; Zebrafish - metabolism; Zebrafish Proteins - genetics; Zebrafish Proteins - metabolism; Multiciliated cell; Multicilin; Zebrafish; Gmnc; E2f4; E2f5; Cilia
• ISSN: 0012-1606; 1095-564X
• DOI: 10.1016/j.ydbio.2018.09.013

Multiciliated cells (MCCs) differentiate arrays of motile cilia that beat to drive fluid flow over epithelia. Recent studies have established two Geminin family coiled-coil containing nuclear regulatory proteins, Gmnc and Multicilin (Mci), in the specification and differentiation of the MCCs. Both Gmnc and Mci are devoid of a DNA binding domain: they regulate transcription by associating with E2f family transcription factors, notably E2f4 and E2f5. Here, we have studied the relative contribution of these two E2f factors in MCC development using the zebrafish embryo, which differentiates MCCs within kidney tubules and the nose. We found that while E2f4 is fully dispensable, E2f5 is essential for MCCs to form in the kidney tubules. Moreover, using a variety of double mutant combinations we show that E2f5 has a more prominent role in MCC development in the zebrafish than E2f4. This contrasts with current evidence from the mouse, where E2f4 seems to be more important. Thus, distinct combinatorial activities of the E2f4 and E2f5 proteins regulate the specification and differentiation of MCCs in zebrafish and mice. •Both E2f4 and E2f5 contribute to multiciliated cell (MCC) formation in zebrafish.•In contrast to mice, E2f5 has a more important role in zebrafish MCC development.•Relative contribution of the E2fs is distinct between pronephros and nasal placode.•The master regulator for MCC development, Gmnc, interacts with both E2f4 and E2f5.