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.

Blood Development “Establishment of a Diamond-Blackfan anemia like (DBAL) model in zebrafish”, by Yiming Ling, Jiaye Wu, Yushi Liu, Panpan Meng, Ying Sun, Dejian Zhao, and Qing Lin; Dev Dyn 253:10, pp. 906–921. https://doi.org/10.1002/dvdy.703. Red blood cells (erythrocytes), which have a typical lifespan of 90–120 days, are essential for oxygen delivery throughout the body. Deficiencies in erythrocyte number or morphology, or hemoglobin levels can result in anemia. Zebrafish, which have transparent embryos, are a powerful model for studying human hematological disorders. In this study, the authors generated epoa-deficient zebrafish as a model of Diamond–Blackfan anemia like (DBAL), which occurs in humans in association with recessive loss-of-function mutations in EPO. EPO is crucial for erythrocyte development and oxygen transport and epoa^szy8/zy8 mutants carrying the human EPO mutation c.530G>A, developed DBAL due to reduced EPO expression. The severe anemia observed in epoa^szy8/zy8 mutant zebrafish can be used to screen drugs for treating epoa-deficiency anemia, and recombinant human EPO significantly improved erythrocyte numbers. Zebrafish epoa models of DBAL are therefore beneficial for in vivo assessments of patient-derived EPO variants, and for developing potential therapeutic approaches for treating DBAL.

Craniofacial and Hair Development “Lineage-specific requirements of Alx4 function in craniofacial and hair development” by Yu Lan, Zhaoming Wu, Han Liu, and Rulang Jiang; Dev Dyn 253:10, pp. 940–948. https://doi.org/10.1002/dvdy.705. The ALX family of transcription factors are key regulators of craniofacial development. Variants in ALX4 have been associated with autosomal dominant parietal foramina and autosomal recessive frontonasal dysplasia with alopecia in humans, but the mechanisms connecting their etiology and pathogenesis remain poorly understood. Alx4 is broadly expressed throughout development, making it difficult to determine its cell-autonomous and non-cell autonomous functions. Here the authors report the generation and characterization of Alx4^fx/fx conditional mice as a valuable new resource for investigating the pathogenic mechanisms underlying ALX4-related developmental disorders and alopecia. Alx4 tissue-specific loss-of-function in neural crest cells and limb bud mesenchyme, results in craniofacial and limb bud developmental defects. Alx4 null mutant mice that survive postnatally exhibit dorsal alopecia, whereas mice lacking Alx4 in neural crest cells display restricted hair loss over the anterior skull. Alx4 is expressed in mesenchymal cells surrounding the developing follicles, in outer root sheath epithelial cells surrounding the hair, and in the dermal papilla. Further study is therefore required to determine which domain of Alx4 is crucial for hair growth and regeneration.

Neural Development “Reduced mTORC1-signaling in progenitor cells leads to retinal lamination deficits” by Christoffer Nord, Iwan Jones, Maria Garcia-Maestre, Anna-Carin Hägglund, and Leif Carlsson; Dev Dyn 253:10, pp. 922–939. https://doi.org/10.1002/dvdy.707. The mammalian central nervous system is remarkable for its anatomical complexity and functional capabilities. Underpinning these properties is neuronal lamination or the organization of distinct neuronal classes into stratified layers. For example, the mouse retina develops from a homogenous pool of retinal progenitor cells into six neuronal and one glial cell type whose cell bodies are laminated within three nuclear layers. Proper development of this tissue architecture requires coordinated cell proliferation, differentiation, and migration of progenitor cells. Here the authors demonstrate that the mammalian target of rapamycin complex 1 (mTORC1) signaling pathway is critical for the precise spatiotemporal regulation of retinal lamination mTOR is assembled from two core proteins (mTOR and Raptor) and associated regulators (PRAS40, mLST8, and Deptor). Tissue-specific ablation of Raptor in retinal progenitor cells resulted in decreased proliferation, increased apoptosis, irregular lamination and stratification, aberrant retinogeniculate topography, and loss of visually mediated behavior. Thus, mTORC1 regulates multiple aspects of retinal progenitor cell biology. This study therefore expands our understanding of the diverse roles of mTORC1 during visual system development and illustrates the conserved role of mTORC1 signaling in histogenesis of the CNS.