Endodermal pouch-expressed dmrt2b is important for pharyngeal cartilage formation.

Linwei Li,Yu Cao,Aihua Mao,Guozhu Ning,Qiang Wang,Peng Wang

doi:10.1242/bio.035444

Abstract

ABSTRACTPharyngeal pouches, a series of outpocketings derived from the foregut endoderm, are essential for craniofacial skeleton formation. However, the molecular mechanisms underlying endodermal pouch-regulated head cartilage development are not fully understood. In this study, we find that zebrafish dmrt2b, a gene encoding Doublesex- and Mab-3-related transcription factor, is specifically expressed in endodermal pouches and required for normal pharyngeal cartilage development. Loss of dmrt2b doesn't affect cranial neural crest (CNC) specification and migration, but leads to prechondrogenic condensation defects by reducing cxcl12b expression after CNC cell movement into the pharyngeal arches. Moreover, dmrt2b inactivation results in reduced proliferation and impaired differentiation of CNC cells. We also show that dmrt2b suppresses crossveinless 2 expression in endodermal pouches to maintain BMP/Smad signaling in the arches, thereby facilitating CNC cell proliferation and chondrogenic differentiation. This work provides insight into how transcription factors expressed in endodermal pouches regulate pharyngeal skeleton development through tissue–tissue interactions.

Highlights

Craniofacial malformations, which occur due to developmental issues of the head, face, and neck, account for approximately one-third of congenital birth defects (DeLuke, 2014)
We find that zebrafish dmrt2b, a gene encoding Doublesex and Mab-3-related transcription factor, is expressed in endodermal pouches and required for normal pharyngeal cartilage development
We show that dmrt2b suppresses crossveinless 2 expression in endodermal pouches to maintain BMP/Smad signaling in the arches, thereby facilitating cranial neural crest (CNC) cell proliferation and chondrogenic differentiation

Summary

Introduction

Craniofacial malformations, which occur due to developmental issues of the head, face, and neck, account for approximately one-third of congenital birth defects (DeLuke, 2014). The neurocranium is derived from both the cranial neural crest (CNC) and mesoderm, while the pharyngeal skeleton, including the jaw and branchial arches, is solely derived from CNC cells (Yelick and Schilling, 2002). Bilateral CNC cells migrate medially with the developing head and from the midbrain and hindbrain as three streams of collective cell populations (mandibular, hyoid and branchial) into the pharyngeal arches to form the pharyngeal cartilages (Couly et al, 1993; Kontges and Lumsden, 1996; Lumsden et al, 1991; Schilling and Kimmel, 1994)

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