Editorial highlights

Abstract

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.

Meet the Editorial Team “An interview with Associate Editor David M. Ornitz, Washington University School of Medicine in St. Louis, St. Louis, MO, USA” by David Ornitz and Paul Trevorrow.¹ For over three decades, Dr. Ornitz's research has focused on the function of fibroblast growth factors (FGFs) in development, physiology, response to injury, and cancer. His graduate training at the forefront of transgenic mouse technology laid the foundations for modeling the genetic pathogenesis of cancer and the discovery of heparan sulfate proteoglycans as essential cofactors for FGF signaling. With a focus on Fgf3, Fgf9, Fgf18, and Fgfr3, Dr. Ornitz has made significant contributions to our understanding of cardiovascular, inner ear, pulmonary, and skeletal biology.

Macrophages, Inflammation, and Cancer “Rodent monocyte-derived macrophages do not express CD163: Comparative analysis using macrophages from living boreoeutherians” by Yoichi Saito, Yukio Fujiwara, Yasuka Yamaguchi, Satomi Tanaka, Kyoko Miura, Yoshiyuki Hizukuri, Kyoko Yamashiro, Yasuhiro Hayashi, Yuta Nakashima and Yoshihiro Komohara.² Macrophages are important for the regulation of inflammation and can be broadly classified into two classes: M1-like macrophages, which induce inflammation; and M2-like macrophages, which function in anti-inflammatory responses, tissue regeneration and repair. Anti-inflammatory, M2-like macrophages express CD163, a scavenger receptor, on their cell surfaces, and a high density of CD163-positive tumor-associated macrophages (TAMs) is thought to correlate with poor prognosis in human patient tumors. However, CD163-positive macrophages only infiltrate the margins of a tumor, not the center, and the authors found that the macrophages that infiltrate tumors, wounds, and inflammatory sites are actually CD-163 negative. Furthermore, the absence of CD-163 expression in monocyte-derived macrophages is shared across the rodent clade. The authors discuss CD163-positive resident macrophages as an important driver of tumor growth irrespective of the animal species or cell type of origin and then suggest that in mice, CD163-positive macrophages originate from a subset of resident macrophages, specifically, fetal liver monocytes/macrophages. CD163 is a conserved protein, and it will be important to elucidate both the molecular and cellular functions of CD163 across a wide variety of diseases and a broad range of animals, including humans, livestock, pets, and other mammals.

Zebrafish Models of Cohesinopathies “Protein turnover downstream of the Nipbl/CRL4 axis contributes to abnormal development in zebrafish embryos” by Annie Sanchez, Niusha Banoukh, Fiona Mensching, Robert Skibbens, and M. Kathryn Iovine.³ Cohesins are protein complexes that mediate DNA tethering, which is important for cell cycle progression, transcriptional regulation, chromosome segregation, and DNA repair. Cohesin mutations often lead to aneuploidy (a hallmark of cancer cells) or severe developmental abnormalities (termed cohesinopathies), such as Roberts Syndrome and Cornelia de Lange Syndrome (CdLS). The majority of CdLS cases are associated with mutations in NIPBL. In this study, knockdown of nipbla/b in zebrafish results in developmental abnormalities resembling cohesinopathies, including craniofacial anomalies. Similar to other models of cohesinopathies, such as esco2 knockdown and smc3 knockdown zebrafish, ddb1 expression was significantly downregulated in nipbla/b knockdown embryos. Interestingly, overexpression of exogenous ddb1 reduced the severity of body size, eye diameter, and otolith defects in nipbla/b knockdown embryos. This supports a model where nipbla/b and other cohesin pathway factors contribute to the transcriptional control of ddb1, thereby modulating CRL4 E3 ligase activity, which perturbs protein degradation, resulting in aberrant accumulation, which disrupts developmental processes.

Bone Development “Dynamics of postnatal bone development and epiphyseal synostosis in the caprine autopod” by Christopher Panebianco, Maha Essaidi, Elijah Barnes, Ashley Williams, Karin Vancíkova, Margot Labberté, Pieter Brama, Niamh Nowlan, and Joel Boerckel.⁴ The anatomy and physiology of bones have evolved to balance strength and mobility, and the skeleton continuously remodels throughout animal growth and development, and mature bone adapts and remodels in response to loading. An animal's ability to ambulate at birth influences the dynamics of postnatal skeletal development, but it has been difficult to distinguish the mechanisms that govern ambulatory loading from those that regulate bone development. This study therefore focused on precocial animals, such as goats, which undergo primary and secondary ossification in preparation for future loading and ambulation from birth through adulthood. In the autopod, cortical bone rapidly densified and thickened until sexual maturity was reached, and the structural distribution correlated with ambulatory loading. Similarly, cortical bone increased in trabecular number and thickness. Metacarpal epiphyses fused postnatally through fibrocartilaginous endochondral ossification, prior to growth plate closure. Together, these data provide new insights into precocial bone development, implicating ambulatory loading in postnatal bone development of precocial animals such as goats.

Endoderm Differentiation and Perineum Formation “Endoderm differentiates into a transient epidermis in the mouse perineum” by Christine Larkins, Daniel Grunberg, Gabriel Daniels, Erik Feldtmann, Martin Cohn.⁵ In eutherian mammals, the openings for the digestive and genitourinary tracts are separated by the perineum, which forms the base of the pelvic floor between the anus and the external genitalia. The perineum is a puzzling example of endoderm contributing to epidermis, as elsewhere in the embryo, the epidermis develops from surface ectoderm. This study examined the fate of the endodermal lineage and the cellular behaviors that underlie development and sexual differentiation of the perineum epidermis. Although the endodermal epidermis is transient, and eventually is replaced by the ectodermal lineage, live imaging, cell tracking, and the expression of markers of the basal, spinous, and granular layers of the epidermis in a spatially organized pattern confirmed the endoderm truly contributes to epidermis. Furthermore, the study suggests that convergent extension may play a key role in the morphogenesis of the perineum epidermis.