Editorial highlights

Every organism is a model organism for understanding development, evolution, disease, and regeneration, and we have only begun to scratch the surface of the interdisciplinary genetic, molecular, cellular, and developmental mechanisms that regulate these biological processes. These “Highlights” denote exciting advances recently reported in Developmental Dynamics that illustrate the complex dynamics of developmental biology.

Sensory Development. “Rspo1 and Rspo3 are required for sensory lineage neural crest formation in mouse embryos” by Takuma Shinozuka, Motoko Aoki, Yudai Hatakeyama, Noriaki Sasai, Hiroshi Okamoto, and Shinji Takada; Dev Dyn 253:4, pp. 435–446. https://doi.org/10.1002/dvdy.659. Wnt/β-catenin signaling plays multiple critical roles during embryonic development and throughout adult homeostasis, and R-spondins (Rspos) are secreted proteins that modulate Wnt/β-catenin signaling. This study documented the expression of all four Rspo genes in the developing mouse spinal cord and found that Rspo1 and Rspo3 are specifically expressed in the roof plate from E9.5 to E18.5. To functionally test for the roles of Rspo1 and Rspo3 in the developing spinal cord, the authors generated mutant embryos defective in either or both of these Rspos. Rspo1-KO and Rspo3-cKO double-mutant embryos displayed defects in specification of Ngn2-positive sensory lineage cells. The results show that although Rspo1 and Rspo3 are dispensable for most developmental processes involving roof plate-derived Wnt ligands, they are critically required for specification of a subtype of neural crest cells. Thus, Rspos modulate Wnt/β-catenin signaling in a context-dependent manner.

Axial Development and Elongation. “Specific CaMKIIs mediate convergent extension cell movements in early zebrafish development” by Jamie McLeod, Sarah Rothschild, Ludmila Francescatto, Haerin Kim, and Robert Tombes; Dev Dyn 253:4, pp. 390–403. https://doi.org/10.1002/dvdy.665. Coordinated inductive and morphogenetic processes establish the vertebrate body plan during gastrulation. Central to this process is convergent extension which narrows the germ layers mediolaterally (convergence) while elongating them anterioposteriorly (extension). Non-canonical Wnts are morphogens that can elevate intracellular Ca²⁺ and activate the Ca²⁺/calmodulin-dependent protein kinase, CaMKII, and promote convergent extension cell movements during vertebrate gastrulation. In this study, the authors demonstrate that zebrafish embryos spatiotemporally express seven CaMKII genes during embryogenesis, two of which camk2b1 and camk2g1, are necessary for convergent extension cell movements. Interestingly, overexpression of CaMKII partially rescued Wnt11 morphant convergent extension phenotypes. Therefore, cyclically activated CaMKII encoded from two genes enables cell migration during the process of convergent extension.

“Elongation of the developing spinal cord is driven by Oct4-type transcription factor-mediated regulation of retinoic acid signaling in zebrafish embryos,” by Tatsuya Yuikawa, Takehisa Sato, Masaaki Ikeda, Momo Tsuruoka, Kaede Yasuda, Yuto Sato, Kouhei Nasu, and Kyo Yamasu; Dev Dyn 253:4, pp. 404–422. https://doi.org/10.1002/dvdy.666. Axial elongation is dependent upon neuromesodermal progenitors (NMPs) which reside in the tail bud and give rise to nerve cells of the spinal cord and various tissues of the paraxial mesoderm. Zebrafish pou5f3 is expressed in the dorsal region of the tail bud during early somitogenesis and then in the posterior-most neural tube during mid-somitogenesis, and pou5f3 mutants exhibit tail elongation defects. Collectively this suggests a role for pou5f3 in the neural specification of tail bud cells. Here, the authors evaluated the importance of pou5f3 in axial extension in CRISPR/Cas9 tamoxifen-inducible pou5f3 mutants and discovered that pou5f3 regulates the levels of retinoic acid and contributes to neurogenesis in the posterior neural tube.

Tooth Development. “Impaired breakdown of Herwig's epithelial root sheath disturbs tooth root development” by Ju-Kyung Jeong, Tak-Heun Kim, Hwajung Choi, and Eui-Sic Cho; Dev Dyn 253:4, pp. 423–434. https://doi.org/10.1002/dvdy.667. Tooth roots are important for mastication and Hertwig's epithelial root sheath (HERS) is recognized as the developmental center for root formation. Consisting of two layers, HERS forms before the appearance of root dentin, and then guides overall root formation by inducing odontoblast differentiation from the dental papilla mesenchymal cells. HERS breakdown results in induction of β-catenin stabilization and formation of epithelial cell rests of Malassez (ERM). The results of this study suggest that Wnt/β-catenin signaling is decreased in HERS for ERM formation during root development. Furthermore, ERM formation is important for further elongation and dentin mineralization of the tooth roots. These findings may provide new insights into the contribution of ERM to root formation.