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.

Limb Development “The limb dorsoventral axis: Lmx1b's role in development, pathology, evolution, and regeneration” by Alejandro Castilla-Ibeas, Sofía Zdral, Kerby Oberg, and Marian Ros. Dev Dyn. 253:9, pp. 798–814. https://doi.org/10.1002/dvdy.695. Limbs, which are crucial for locomotion, are thought to have evolved from fins in an aquatic ancestor as an adaptation to shallow water. Over time, limbs acquired complex characteristics built upon anterior-posterior, proximal-distal, and dorsal-ventral axes. Although limb development and patterning has been well studied, we still have much to learn about the dorsal-ventral axis. The dorsal domain of the limb houses the extensor muscles, ligaments, tendons, nerves, and vessels, whereas the ventral region contains flexor muscles among other tissues and structures. This review discusses our current understanding of dorsal-ventral patterning of the limb, bringing together the results of classic experiments with modern research, concepts, and interpretations. With an emphasis on Lmx1b, which specifies dorsal character and subsequently fate, the authors consider the role of dorsal-ventral patterning in the evolution of paired appendages and the association of variants in LMX1B in association with nail-patella syndrome. Finally, the role of dorsoventral patterning and polarity in digit tip regeneration in mammals is also considered further informing our understanding of limb function and evolutionary adaptations.

Neurodevelopment “Disruption of Fuz in mouse embryos generates hypoplastic hindbrain development and reduced cranial nerve ganglia” by Carlo Donato Caiaffa, Yogeshwari Ambekar, Manmohan Singh, Ying Linda Lin, Bogdan Wlodarczyk, Salavat Aglyamov, Giuliano Scarcelli, Kirill Larin, and Richard Finnell. Dev Dyn. 253:9, pp. 846–858. https://doi.org/10.1002/dvdy.702. Neurulation is the process of neural tube formation from the neural plate, which subsequently forms the central nervous system, while also contributing to the peripheral nervous system. Perturbation of the early steps of neurulation can lead to neural tube defects, which are one of the most common birth defects, affecting about two in every 100 live births, or about 300,000 cases per year worldwide. Genetic mutations, environmental factors, and nutritional imbalances critically underpin the pathogenesis of most neural tube defects. The Fuz gene forms part of a macromolecular planar polarity effector required for ciliogenesis, and consequently, Fuz knockout mice exhibit exencephaly of spina bifida. Underpinning these phenotypes, Fuz mutant embryos exhibit hypoplastic cranial and paravertebral ganglia, and a smaller hindbrain, in association with persistent reduction of ventral neuroepithelial stiffness in the notochord. Fuz is required for sustaining neuroepithelial integrity during neural tube closure and development. This work shows for the first time that abnormal hindbrain morphology and persistent loss of neuroepithelial stiffness precede exencephaly in Fuz mutant mouse embryos.

Whale Embryogenesis “Protein signaling and morphological development of the tail fluke in the embryonic beluga whale” by Lia. Gavazzi, Manas Nair, Robert. Suydam, Sharon Usip, Hans Thewissen, and Lisa Cooper. Dev Dyn. 253:9, pp. 859–874. https://doi.org/10.1002/dvdy.704. During the land-to-sea transition of cetaceans (whales, dolphins, and porpoises), the hindlimbs were lost and replaced by an elaborate tail fluke. Modern cetaceans utilize flukes for lift-based propulsion, but nothing is known about the molecular origins of underpinning of their anatomical development and function during embryogenesis. This study tests the hypothesis that classic well recognized signals associated with outgrowth and patterning of tetrapod limbs, also regulate tail fluke development. Focusing on the beluga whale (Delphinapterus leucas) as a case study, the authors initially show that bilaterally symmetrical flukes of cetaceans are supported by caudal tail vertebrae and dense connective tissues that are enveloped by skin. Next the authors show that epidermal WNT and FGF signals, and mesenchymal/epidermal SHH and GREM signals, mimic the patterns characteristic of vertebrate limb development. This implies that the genes and proteins that regulate limb outgrowth and patterning also govern the outgrowth and shape of the evolutionarily novel tail fluke appendage in cetaceans. This body of work therefore provides key insights into the evolution and development of a novel organ.