Highlights in DD

Abstract

“Highlights” calls attention to exciting advances in developmental biology that have recently been reported in Developmental Dynamics. Development is a broad field encompassing many important areas. To reflect this fact, the section spotlights significant discoveries that occur across the entire spectrum of developmental events and problems: from new experimental approaches, to novel interpretations of results, to noteworthy findings utilizing different developmental organisms. Moving on (Evolution of Vertebrate Appendicular Structures: Insight From Genetic and Palaeontological Data by Amir Ali Abbasi, Dev Dyn 240:1005–1016). How fins evolved into limbs is one of the quintessential examples of morphological evolution, the study of the diversification of body form over time. In this Special Issue on limb development, Abbasi assembles information from molecular biology, genetics, comparative biology, and paleontology to illustrate key morphological and molecular events that enact this grand change. One remaining mystery is how the distal bones of a primordial fin/limb transformed into modern toes and fingers. Chipping away at the problem, he describes how certain molecular pathways (i.e., Shh, 5′Hoxd cluster) are involved in fin/limb patterning both pre- and postevolutionary digit formation. He further explains how the morphological advancement could be triggered by molecular changes in cis-regulatory elements of conserved genes that alter sites and/or timing of activity. His careful analysis of what is known helps him to pinpoint specific areas of research that could help fill the morphological gap. These insights should enable researchers to hit the ground running. Tales of the pinkie (HMGB Factors Are Required for Posterior Digit Development Through Integrating Signaling Pathway Activities by Junji Itou, Noboru Taniguchi, Isao Oishi, Hiroko Kawakami, Martin Lotz, Yasuhiko Kawakami, Dev Dyn 240:1151–1162) Hmgb1−/−;Hmbg2+/− mice have a subtle forelimb phenotype, loss of the most posterior digit (analogous to the human pinkie finger). Although the defect may seem minor, it speaks volumes about the role of these chromatin factors in limb patterning. The phenotype mimics reduced signaling of Sonic Hedgehog (Shh) in the limb bud, and Itou et. al, verify that Hmgb1−/−;Hmbg2+/− also have this molecular defect. How, then, might HMGB factors regulate limb Shh? The authors suspect the interaction is indirect. The largely redundant HMGB1 and 2 bind DNA nonsequence specifically and alter chromatin architecture, and also facilitate Wnt/β-catenin signaling. In light of the latter finding, they are surprised to find that dorsal ectoderm Wnt7a signaling, which regulates posterior Shh, is normal in Hmgb1−/−;Hmbg2+/− limbs. They do, however, find that Wnt/β-catenin targets display reduced expression in the posterior mesenchyme, suggesting the tissue is an uncharacterized region of Wnt7a signaling. Supporting this idea, Hmbg1 and 2 also facilitates Wnt/β-catenin signaling in numerous tissues in the developing zebrafish, including the pectoral fin, a forelimb homolog. In addition to a role in Wnt/β-catenin signaling, there is also evidence that HMGB factors modulate BMP signaling. The authors discuss how proper development of the little finger may hinge on integration of these pathways by HMGB 1 and 2. Golden eggs (Identification of Spontaneous Mutations Within the Long-Range Limb-Specific Sonic Hedgehog Enhancer (ZRS) That Alter Sonic Hedgehog Expression in the Chicken Limb Mutants oligozeugodactyly and Silkie Breed by Sarah A. Maas, Takayuki Suzuki, and John F. Fallon, Dev Dyn 240:1212–1222) What might be considered an oddity to an animal breeder can be a goldmine to a biologist. So it is with the spontaneous oligozeugodactyly (ozd) chicken mutant, which lacks all but one digit on each foot, and the preaxial polydactylous (PPD) Silke breed with extra digits. Because mutations in the evolutionarily conserved zone of polarizing activity (ZPA) regulatory sequence (ZRS)—which controls posterior limb Shh expression and anteroposterior limb patterning—has been implicated in human PPD, Maas et al. examined the ZRS in the two strains. Eureka! While ozd chickens lack most of the ZRS enhancer, the Silkie ZRS has a single point mutation within it. To further investigate ZRS function, the group devised the first enhancer assay that works in the developing limb bud in vivo. They find that although the ozd mutant does not express Shh, the wild-type ZRS enhancer drives expression of β-galactosidase (β-gal) in a small group of cells within the pre-ZPA, suggesting they are still ZPA competent. The Silkie ZRS sequence drives β-gal expression that is expanded to the anterior domain, mirroring the ectopic Shh expression observed in this breed. Together the results suggest the ZRS receives both positive and negative input. The next pot of gold goes to the one who determines how factors that prepattern the limb act upon the ZRS to fine-tune Shh expression.