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. Ocular Development and Disease. “Zebrafish model of RERE syndrome recapitulates key ophthalmic defects that are rescued by small molecule inhibitor of shh signaling” by Aman George, Jerry Lee, James Liu, Suzie Kim and Brian Brooks; DevDyn 252:4, pp. 495-509; https://doi.org/10.1002/dvdy.561. Mutations in the human RERE gene (ATROPHIN 2, OMIM *605226) are associated with a neuro-developmental disorder that includes ophthalmic, cardiac, genitourinary and hearing defects. This study demonstrates that rerea mutant (babyface) zebrafish recapitulate the optic fissure closure defects that result from loss of RERE function in humans. Interestingly, the RERE gene acts as a transcriptional corepressor in various nuclear receptor signaling pathways, and the optic fissure phenotype is associated with expansion of proximal retinal optic stalk in concert with deregulated shh signaling. Consistent with this model, inhibiting shh signaling can rescue the coloboma phenotype. Craniofacial Biology. “Frem1 activity is regulated by Sonic Hedgehog signaling in the cranial neural crest mesenchyme during midfacial morphogenesis” by Matthew McLaughlin, Miranda Sun, Tyler Beames, Austin Steward, Joshua Theisen, Hannah Chung, Joshua Everson, Ivan Moskowitz, Michael Sheets and Robert Lipinski; DevDyn 252:4, pp. 483-494; https://doi.org/10.1002/dvdy.555. The human face exhibits remarkable variation, and is also highly prone to developmental anomalies. The Frem/Fras family of extracellular matrix proteins has been implicated in regulating face shape variation as well as being mutated in the pathogenesis of disorders such as Manitoba-oculo-tricho-anal bifid nose with or without anorectal and renal anomalies, and Fraser syndromes. This study examined the activity of Frem1 during facial morphogenesis and identified Sonic Hedgehog (Shh) as an upstream regulator that promotes the proliferation of neural crest cells. Shh-Frem1 signaling is disrupted during the pathogenesis of midface hypoplasia, which provides deeper insights into the mechanisms underlying congenital craniofacial anomalies, and variation in midfacial morphogenesis. Organogenesis. “Foxd1 is required for 3D patterning of the kidney interstitial matrix by Sarah Lipp, Kathryn Jacobson, Andrew Schwaderer, David Hains and Sarah Calve; DevDyn 252:4, pp. 463-482; https://doi.org/10.1002/dvdy.545. The extracellular matrix (ECM) comprises a complex network of proteins and glycosaminoglycans that functions as a reservoir of growth factors, while also providing structural integrity and support during kidney development. This study combined 3D imaging and proteomics to investigate the role of Foxd1 in stromal cells, which are responsible for synthesizing the interstitial extracellular matrix, and document how the extracellular matrix dynamically changes during normal murine kidney development and in a model of kidney hypodysplasia. Changes in interstitial extracellular matrix corresponded to disruptions in stromal cell patterning, which helps to shed light on why human patients with connective tissue disorders have an increased incidence of kidney cysts and congenital anomalies of the kidney and urinary tract.